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EC number: 224-116-8 | CAS number: 4203-89-8
- 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
Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.882 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 50
- Dose descriptor starting point:
- NOAEL
- Value:
- 50 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 44.079 mg/m³
- Explanation for the modification of the dose descriptor starting point:
There are no relevant data for repeated exposure by inhalation. The systemic NOAEL of 50 mg/kg/day from OECD 422 repeat dose oral study with rats (6 - 8 weeks) was used for DNEL derivation. Assuming an oral /inhalation absorption of 0.5 a dose descriptor NOAEC of 44.079 mg/m3 was derived as the modified starting point. This study is a well conducted repeated dose study in rats and is of good quality (GLP, OECD guideline). For details, please see under "Additional information - Workers".
- AF for dose response relationship:
- 1
- Justification:
- per REACH Guidance. The dose response relationship is considered unremarkable, therefore no additional factor is used.
- AF for differences in duration of exposure:
- 4
- Justification:
- Per REACH Guidance. (OECD 422 study duration was 6-8 weeks), less than subhronic study duration, but more than subacute study duration.
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- Not applicable for inhalation DNEL, per REACH Guidance. Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.
- AF for other interspecies differences:
- 2.5
- Justification:
- per REACH Guidance
- AF for intraspecies differences:
- 5
- Justification:
- per REACH Guidance. Default value for the relatively homogeneous group,"Worker" is used.
- AF for the quality of the whole database:
- 1
- Justification:
- per REACH Guidance. Default value
- AF for remaining uncertainties:
- 1
- Justification:
- per REACH Guidance. Default value. No further AF are required as a conservative approach was used.
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 0.5 mg/kg bw/day
- Most sensitive endpoint:
- developmental toxicity / teratogenicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 50
- Dose descriptor starting point:
- NOAEL
- Value:
- 50 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 100 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
There are no specific experimental data on repeated dermal exposure or on dermal absorption. The systemic NOAEL of 50 mg/kg bw/day from OECD 422 repeat dose oral study in rats was used. Assuming a dermal absorption of 50% (taking into account the physico-chemical properties of molecular weight and water solubility and logKow), a dose descriptor of 100 mg/kg bw/d was derived as the starting point.This study was used for DNEL derivation as it is of good quality (GLP, OECD). Details can be found under "Additional information - Workers"
- AF for dose response relationship:
- 1
- Justification:
- per REACH Guidance
- AF for differences in duration of exposure:
- 4
- Justification:
- Per REACH Guidance. (OECD 422 study duration was 6-8 weeks)
- AF for interspecies differences (allometric scaling):
- 4
- Justification:
- per REACH Guidance (allometric scaling)
- AF for other interspecies differences:
- 2.5
- Justification:
- per REACH Guidance
- AF for intraspecies differences:
- 5
- Justification:
- per REACH Guidance. Default value
- AF for the quality of the whole database:
- 1
- Justification:
- per REACH Guidance. Default value
- AF for remaining uncertainties:
- 1
- Justification:
- per REACH Guidance. Default value
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- sensitisation (skin)
- Route of original study:
- Oral
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Acute/short term exposure
- Hazard assessment conclusion:
- high hazard (no threshold derived)
- Most sensitive endpoint:
- skin irritation/corrosion
Workers - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - workers
Phys-Chem properties of CAS# 4203-89-8 ( 2-(1-oxa-4-azaspiro[4.5]dec-4-yl)ethyl methacrylate)
Physical state | Liquid |
Molecular Weight | 253.34 |
Log Kow , Experimental | 3.2 at 25 °C |
Vapor pressure | 0.0485 Pa at 25 °C |
Water solubility, measured,25oC | Not possible to measure; 918.6 g/L (calculated per EPISuite) |
Eye, in vivo | Non irritant |
Skin, in vivo | Corrosive, Cat 1 |
Skin sensitization, QSAR predictions | Sensitizer, Cat 1 |
NOAEL (oral, rat, m/f, OECD 422) | 50 mg/kg bw/d |
Absorption through Inhalation: The test substance has a molecular weight of 253.3, and a log Kow of 3.2. Any lipophilic compound may be taken up by micellar solubilization but this mechanism may be of particular importance for highly lipophilic compounds (log P>4), particularly those that are poorly soluble in water (< 1mg/L) that would otherwise be poorly absorbed. Since the oral absorption study indicated some systemic toxicity, the potential for absorption through inhalation is likely. However, the vapor pressure (0.0485 Pa at 25oC) of the test item is very low. Therefore, inhalation is not expected to be a major route of exposure / absorption. The respiratory absorption is considered to be 100% for DNEL calculations.
Dermal absorption: For molecular weights above 500 and log P values below -1 or above 4 a conservative default absorption factor at 10% cutaneous absorption has been set (EC 2007). The test substance has a molecular weight of 253.3, and a log Kow of 3.2. Any lipophilic compound may be taken up by micellar solubilization but this mechanism may be of particular importance for highly lipophilic compounds (log P>4), particularly those that are poorly soluble in water (< 1mg/L) that would otherwise be poorly absorbed. Low vapor pressure (0.0485 Pa at 25degrees C) may favor dermal uptake. The substance also has skin corrosive property (in rabbits) making it more available to the deeper layers of the skin. It is considered to be a skin sensitizer by by QSAR predictions. Based on all these factors, the dermal absorption is therefore considered to be 50%.
In a GLP, OECD 422“Combined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening Test”, study, daily oral administration of2 -(1 -oxa-4 -azaspiro[4.5]dec-4 -yl)ethyl methacrylate
(CAS 4203 -89 -8) to Wistar Han™:RccHan™:WIST strain rats for 6 -8 weeks (including 2 weeks pre-pairing, gestation and early lactation for females) at dose levels 50, 150 and 375 mg/kg bw/day resulted inthe following findings:
Treatment of males at 375 mg/kg bw/day was associated with lower body weight (BW) gains and inferior food conversion efficiency, compared to control, changes for hematology and blood chemistry parameters suggestive of mild anemia and liver and kidney effects and increased BW-relative liver and kidneys weights. Histopathology revealed minimal tubular vacuolation of the kidneys. Collectively these findings precluded this dosage from representing a No Observed Adverse Effect Level (NOAEL) for male systemic toxicity. Treatment at 150 mg/kg bw/day was associated with inferior BW gain, compared to control, changes in hematology parameters and blood chemistry parameters suggestive of mild anemia and effects on the liver and kidney, and increased BW relative liver and kidneys weights. Histopathological examination revealed minimal tubular vacuolation of the kidneys. These findings occurred to a lesser extent than observed at 375 mg/kg bw/day, and a dosage of 150 mg/kg bw/day was considered to represent the Lowest Observed Adverse effect Level (LOAEL) for male systemic toxicity. At 50 mg/kg bw/day, there were no effects on BW gains or food consumption apparent and only occasional changes for hematology and blood chemistry parameters. While increased BW relative liver and kidneys weights were apparent, treatment related histopathological findings were restricted to a low incidence of minimal tubular vacuolation of the kidneys. The extent of effects at this dosage were considered insufficient to represent an adverse effect and, as such,this dosage was regarded as the NOAEL for male systemic toxicity.
Treatment of females at 375 mg/kg bw/day was generally associated with lower BW gains throughout most of the study, including pre-mating, gestation and late lactation. Food conversion efficiency was inferior during the first week of treatment and food consumption was lower throughout gestation. Effects on hematology and blood chemistry parameters were minor but increases in BW-relative liver and kidney weights were apparent. Histopathology reveal minimal tubular vacuolation and, more significantly, multifocal basophilic tubules of the kidneys; the latter finding was considered to be adverse and clearly precluded this dosage from being regarded as a NOAEL for female systemic toxicity. At 150 mg/kg bw/day, inferior BW gain and food conversion efficiency was apparent during the 2 week pre-mating phase with lower BW gain continuing throughout gestation. Effects on hematology and blood chemistry parameters were minor. Increases in BW- relative liver and kidney weights were apparent, but treatment related histopathological changes were restricted to minimal tubular vacuolation of the kidneys. This dosage probably represents the LOAEL for female systemic toxicity. At 50 mg/kg bw/day, there were no effects on BW gain and only isolated differences from control for hematology and blood chemistry parameters. Increased BW-relative liver and kidneys weights were observed but there were no treatment related histopathological findings. The extent of effects at this dosage were considered insufficient to represent an adverse effect and, as such, thisdosage was regarded as the NOAEL for female systemic toxicity.
At 375 mg/kg bw/day, there was an increased incidence of females with extended gestation length and a reduction in the number of implantations. Despite the lower number of implantations, early post-natal survival of the offspring was inferior to control and whilst offspring survival improved after Day 4 of age, BW gains of the offspring was inferior to control. No obvious morphological changes were apparent for the offspring. At 150 mg/kg bw/day, there were no effects apparent for gestation length or for the survival and growth of the offspring. This dosage therefore represents a clear NOAEL and, probably alsorepresents a NOEL, for reproduction and the survival, growth and development of the offspring.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
Local effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
General Population - Hazard via oral route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- no hazard identified
Acute/short term exposure
- Hazard assessment conclusion:
- no hazard identified
DNEL related information
General Population - Hazard for the eyes
Local effects
- Hazard assessment conclusion:
- no hazard identified
Additional information - General Population
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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