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EC number: 223-228-4 | CAS number: 3775-90-4
- 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
Endpoint summary
Administrative data
Description of key information
The only repeat dose study available on 2-tert-butylaminethyl methacrylate is an OECD 422 repeated dose toxicity oral study, via the drinking water. The NOAEL from this study can also be used to calculate DNELs for the dermal and inhalation routes. Testing is not scientifically justified for these routes due to the corrosive properties of 2-tert-butylaminethyl methacrylate and the limited possibility of exposure by these routes in the workplace.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Remarks:
- combined repeated dose and reproduction / developmental screening
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Guideline study without detailed documentation. Peer-reviewed database.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- GLP compliance:
- yes
- Specific details on test material used for the study:
- Test substance 99.9% purity, Sanyo-Kasei. Co
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Details on species / strain selection:
- Rats supplied by Charles River Japan
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Rats were purchased at 7 weeks of age. After quarantine and acclimatisation for 7 days
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- Males: 43 days
Females: from 14 days before mating to day 3 of lactation (41 -52 days) - Frequency of treatment:
- once daily
- Remarks:
- Doses / Concentrations:
0 (Vehicle), 40, 200, 1000 mg/kg/day
Basis:
actual ingested - No. of animals per sex per dose:
- 12
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: As the LD50 value of > 2000 mg/kg was known, a preliminary test to decide the highest dose level at 30, 100, 300, and 1000 mg/kg/day for 14 days was conducted. At 1000 mg/kg/day, decrease of body weight in males and suppression of body weight increase in females were observed. Then the highest dose level for the test was set at 1000 mg/kg/day.
- Post-exposure period: 1 day - Details on results:
- MALES:
At 1000 mg/kg/day, no deaths occured. Clinical observations revealed late onset of twitching, chronic convulsion and suppression of body weight gain. The histopathological examinations revealed a degeneration of nerve fibers in the brain and spinal cord, hyperplasia of the mucosa, edema and inflammatory cell infiltration in the forestomach and increased kidney and liver weights without histopathological correlates. Hematological and blood chemical examinations revealed a slight increase in BUN and slight anemic changes such as decreases in erythrocyte counts, hemoglobin concentration and hematocrit value, associated with a significant increase in reticulocyte ratio.
At 200 mg/kg/day, no adverse effects except for slight anemic changes such as decrease in hemoglobin concentration and hematocrit value with
increase in reticulocyte ratio were observed. However, the severities of these slight anemic changes were considered toxicologically insignificant.
At 40 mg/kg/day, no effects were observed.
FEMALES:
At 1000 mg/kg/day, 3 females out of 12 died. By clinical observations, late onset of twitching, chronic convulsion, suppression of body weight gain and a decrease in food consumption during lactation period were observed. Histopathological examinations revealed a degeneration of nerve fibers in
the brain and the spinal cord, a hyperplasia of the mucosa in the gastric tract, edema and inflammatory cell infiltrations in the forestomach, and an atrophy of the thymus. Also the increases in the weight of the kidney and the adrenals without histopathological changes were observed.
At 200 mg/kg/day no effects were observed.
At 40 mg/kg/day no effects were observed. - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 200 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- food consumption and compound intake
- haematology
- histopathology: non-neoplastic
- mortality
- neuropathology
- Dose descriptor:
- NOEL
- Effect level:
- 40 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- body weight and weight gain
- food consumption and compound intake
- haematology
- neuropathology
- Dose descriptor:
- NOEL
- Effect level:
- 200 mg/kg bw/day (actual dose received)
- Sex:
- female
- Basis for effect level:
- body weight and weight gain
- food consumption and compound intake
- mortality
- neuropathology
- Critical effects observed:
- not specified
- Conclusions:
- According to this study, the NOAEL for oral (gavage) repeated dose toxicity in rats is considered to be 200 mg/kg/day for both sexes. The NOELs for repeated dose toxicity are considered to be 40 mg/kg/day for males and 200 mg/kg/day for females.
- Executive summary:
The test substance was studied for oral (gavage) toxicity in rats in an OECD combined repeated dose and reproductive/developmental toxicity screening test at doses of 0, 40, 200 and 1000 mg/kg/day. The study was conducted in compliance with GLP.
Three females died in the 1000 mg/kg group. Soiled tail, twitching, chronic convulsion and suppression of body weight gain in both sexes, and a decrease in food consumption in females were also observed in the late period of administration in this group. Histopathological examination revealed degeneration of nerve fibers in the brain and spinal cord, and hyperplasia of the mucosa, edema and inflammatory cell infiltration in the forestomach in both sexes, and atrophy of the thymus in females in the 1000 mg/kg group. Increases in organ weights without histopathological changes were observed for the kidneys of both sexes, the livers of males, and the
adrenals of females in this group. BUN was slightly increased in males in the same group. Slight anemic changes were observed in males of the 200 and 1000 mg/kg groups.
Conclusion: According to this study, the NOAEL for oral (gavage) repeated dose toxicity in rats is considered to be 200 mg/kg/day for both sexes. The NOELs for repeated dose toxicity are considered to be 40 mg/kg/day for males and 200 mg/kg/day for females.
Reference
Hematological examination results in male rats (mean ± SD):
Dose mg/kg) |
0 |
200 |
1000 |
No. of males |
12 |
12 |
11 |
RBC (10000/µl) |
881.7 ± 43.6 |
859.8 ± 36.7 |
821.6 ± 34.1** |
Hematocrit (%) |
46.73 ± 2.45 |
44.84 ± 1.26* |
41.72 ± 1.97** |
Hemoglobin (g/dL) |
15.91 ± 0.69 |
15.28 ± 0.40* |
14.24 ± 0.74** |
Reticulocytes (‰) |
17.81 ± 2.61 |
21.56 ± 3.57* |
24.84 ± 3.75** |
* = p<0.05, ** = p<0.01
_
Major histopathological findings in male rats:
Dose (mg/kg) |
0 |
200 |
1000 |
No. of males |
12 |
12 |
11 |
Findings in stomach: |
|||
Slight dilatation, gastric gland |
0 |
0 |
0 |
Slight edema |
0 |
0 |
7** |
Slight hyperplasia, squamous, forestomach diffuse |
0 |
0 |
11** |
Slight inflammatory cell infiltration, forestomach |
0 |
0 |
10** |
Slight ulcer, forestomach |
0 |
0 |
0 |
Slight ulcer, glandular stomach |
0 |
0 |
0 |
Findings in brain: |
|||
Slight degeneration, nerve fiber |
0 |
0 |
3 |
Findings in spinal cord: |
|||
Slight degeneration, nerve fiber |
0 |
0 |
8** |
** = p<0.01
_
Major histopathological findings in female rats:
Dose (mg/kg) |
0 |
200 |
1000 |
||
Surviving |
Deada) |
Surviving |
Deadb) |
||
No. of females |
11 |
1 |
12 |
9 |
3 |
Findings in stomach: |
|||||
Slight dilatation, gastric gland |
0 |
0 |
0 |
0 |
0/2 |
Slight edema |
0 |
0 |
0 |
2 |
1/2 |
Slight hyperplasia, squamous, forestomach diffuse |
0 |
0 |
0 |
9** |
2/2 |
Slight inflammatory cell infiltration, forestomach |
0 |
0 |
0 |
5** |
1/2 |
Slight ulcer, forestomach |
0 |
0 |
0 |
1 |
0/2 |
Slight ulcer, glandular stomach |
0 |
0 |
0 |
0 |
1/2 |
Findings in brain: |
|||||
Slight degeneration, nerve fiber |
0 |
0 |
0 |
4 |
0 |
Findings in spinal cord: |
|||||
Slight degeneration, nerve fiber |
0 |
0 |
0 |
6** |
0 |
a) One female died of dystocia at gestation day 23
b) Dead animals were observed at days 26 and 38 after administration
** = p<0.01
Endpoint conclusion
- Endpoint conclusion:
- adverse effect observed
- Dose descriptor:
- NOAEL
- 200 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- There is no repeat dose oral dosing study for 2-tert-butylaminoethyl methacrylate but there is Klimisch 2 OECD422 repeat dose, gavage oral dosing study in rats on a read across substance 2-(dimethylamino)ethyl methacrylate CAS No 2867-47-2. A NOAEL of 200 mg/kg bodyweight/day was established, it is considered acceptable to use this value for read across to establish DNELs.
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
- Quality of whole database:
- The requirement for a repeat dose inhalation study is waived due to the availability of a Klimisch 2 OECD422 study by the oral route and the technical difficulties of carry out an inhalation study with a corrosive substance. The oral NOAEL with the additional assessment factor of 2 can provide an adequate systemic DNEL.
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
- Quality of whole database:
- There is no inhalation study available for 2-tert-butylaminethyl methacrylate. Due to the limited potential for inhalation exposure and the ethical considerations in performing an inhalation study with a test substance that is corrosive to skin and eyes indicates, it is not scientifically justified to perform additional animal tests to establish a NOAEL for local effects in the respiratory tract.
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
- Quality of whole database:
- No repeat dose dermal study is available for 2-tert-butylaminethyl methacrylate or the read across substance 2-(dimethylamino)ethyl methacrylate but the use of the oral NOAEL will allow the calculation of systemic dermal DNELs. It is not considered scientifically justified to carry out test. The data base is adequate for the calculation of the DNELs
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
- Quality of whole database:
- There is not study available on 2-tert-butylaminethyl methacrylate or the read across substance 2-(dimethylamino)ethyl methacrylate, to determine a NOAEL for local dermal effects, as the corrosive and skin sensitizing properties of 2-tert-butylaminethyl methacrylate require the use of gloves and protective clothing, the potential for skin contact will be minimized. The available information is sufficient for the safe use of 2-tert-butylaminethyl methacrylate.
Additional information
There is no repeat dose oral dosing study for 2-tert-butylaminoethyl methacrylate but there is Klimisch 2 OECD422 repeat dose, gavage oral dosing study in rats on a read across substance 2-(dimethylamino)ethyl methacrylate CAS No 2867-47-2. Justification for the read across is attached in Section 13. In this OECD422 study 2-(dimethylamino)ethyl methacrylate produced a variety of effects at the 1000 mg/kg bodyweight/day highest dose including the deaths of 3/12 of the females. The middle dose of 200mg/kg bodyweight/day was a NOAEL for both males and females, with the males showing some very minor differences in haemoglobin concentration and haematocrit but these were considered toxicologically insignificant, i.e. not an adverse effect. This NOAEL of 200 mg/kg bodyweight/day is for the parental animals after 43 days dosing in males and at 41-52 days dosing in females (to day 5post partum) which will allow the calculation of DNELs.
There are no studies for2-tert-butylaminethyl methacrylate or the read across substance2-(dimethylamino)ethyl methacrylate by the inhalation or dermal routes of exposure. The requirement for a repeat dose inhalation study is waived due to the availability of a Klimisch 2 OECD422 study by the oral route and the technical difficulties of carry out an inhalation study with a corrosive substance. The oral NOAEL with the additional assessment factor of 2 can provide an adequate systemic DNEL. Also there is no repeat dose dermal study available but the use of the oral NOAEL will allow the calculation of systemic dermal and inhalation DNELs with the appropriate assessment factors. It is not considered scientifically justified to carry out test by these routs due to the corrosive properties of the 2-tert-butylaminethyl methacrylate. The data base is adequate for the calculation of the DNELs.
Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
There is no repeat dose oral dosing study for 2-tert-butylaminoethyl methacrylate but there is Klimisch 2 OECD422 repeat dose, gavage oral dosing study in rats on a read across substance 2-(dimethylamino)ethyl methacrylate CAS No 2867-47-2. Justification for the read across is attached in Section 13. In this OECD422 study 2-(dimethylamino)ethyl methacrylate produced a variety of effects at the 1000 mg/kg bodyweight/day highest dose including the deaths of 3/12 of the females. The middle dose of 200mg/kg bodyweight/day was a NOAEL for both males and females, with the males showing some very minor differences in haemoglobin concentration and haematocrit but these were considered toxicologically insignificant, i.e. not an adverse effect. This NOAEL of 200 mg/kg bodyweight/day is for the parental animals after 43 days dosing in males and at 41-52 days dosing in females (to day 5 post partum) which will allow the calculation of DNELs.
Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
We do not have any repeat exposure inhalation study for 2-tert-butylaminoethyl methacrylate, but there is Klimisch 2 OECD422 repeat dose, gavage oral dosing study in rats on a read across substance 2-(dimethylamino)ethyl methacrylate CAS No 2867-47-2. Inhalation is not expected to be a significant route of exposure due to the containment required as any vapour generated would be irritant/corrosive. Testing of corrosive substances by inhalation would be technically difficult as none corrosive exposure would have to be established. The additional factor of 2 as recommended by ECHA, when using oral data to calculate an inhalation long term systemic DNEL, assumes 100% absorption by inhalation and 50% by the oral route. Based on this, using the REACH guidance a DNEL for systemic effects from inhalation can be calculated for the oral NOAEL. Therefore it is not scientifically justified to carry out an inhalation study; this avoids the use of additional animals.
Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
We have no study for local effects in the respiratory tract on 2-tert-butylaminoethyl methacrylate. 2-tert-butylaminoethyl methacrylate is corrosive to skin and eyes and therefore inhalation would be expected to cause local irritant effects in the upper respiratory tract. As 2-tert-butylaminoethyl methacrylate is handled as a monomer in contained inhalation exposure. Due to the limited potential for inhalation exposure and the ethical considerations in performing an inhalation study with a test substance that is corrosive to skin and eyes indicates, it is not scientifically justified to perform additional animal tests to establish a NOAEL for local effects in the respiratory tract.
Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
There is no dermal repeat dose study for 2-tert-butylaminethyl methacrylate, however there is an oral study Repeated dose toxicity OECD 422 study available on the read across substance 2-(dimethylamino)ethyl methacrylate. REACH guidance allows for the calculation of dermal DNELS for systemic effects from the Oral NOAEL. As for 2-tert-butylaminethyl methacrylate is classified as a skin sensitizer and corrosive to skin gloves and protective clothing will be required when handling it so dermal exposure should be minimized. Therefore as dermal systemic DNELS can be calculated from the oral NOAEL and there are ethical concerns about a repeat dose dermal study for a corrosive chemical, it is not scientifically justified to perform such a test. Dermal repeat dose testing will be waived.
Justification for selection of repeated dose toxicity dermal - local effects endpoint:
There is no specific test data available to establish a NOAEL for 2-tert-butylaminethyl methacrylate, while some work was done to establish doses within the guinea pig skin sensitisation study where 50% was used as the challenge dose. This is not considered suitable for defining a NOAEL for local effects in the skin. 2-tert-butylaminethyl methacrylate is classified as a skin sensitizer and as corrosive to skin, local effects on the skin would be expected to be irritancy/corrosion, therefore the use of appropriate gloves and protective clothing will be required, which will minimize the potential for skin contact. Therefore it is not necessary or scientifically justified to perform an animal study.
Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: stomach; neurologic: central nervous system
Justification for classification or non-classification
Classification for Specific Target Organ Toxicity STOT, by the EU CLP(GHS) guideline requires serious adverse effects on organs at dose levels of less than 100mg/kg bodyweight/day in a 90 day study or <300mg/kg bodyweight/day in a 28 day study. In the OECD 422 study the duration was 43 days for males and 5 day post partum for the females (in excess of 41 days). These values for STOT could therefore be considered to be between the 28 and 90 day i.e. less than 200 mg/kg bodyweight/day. The OECD 422 showed no adverse effects that could be considered to be STOT at the NOAEL dose of 200mg/kg bodyweight/day. Therefore there were no effects that would require classification for STOT
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