Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
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
Short-term toxicity to aquatic invertebrates
Administrative data
Link to relevant study record(s)
- Endpoint:
- short-term toxicity to aquatic invertebrates
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Experimental start date 06 June 2017. Experimental completion date 12 April 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)
- Deviations:
- yes
- Remarks:
- please see nay other information on materials and methods section
- Qualifier:
- according to guideline
- Guideline:
- EU Method C.2 (Acute Toxicity for Daphnia)
- Deviations:
- yes
- Remarks:
- please see nay other information on materials and methods section
- GLP compliance:
- yes (incl. QA statement)
- Specific details on test material used for the study:
- Batch: 1609501020
Purity: 94.5%
Physical state/Appearance: Extremely pale yellow slightly viscous liquid
Expiry Date: 05 October 2018
Storage Conditions: Approximately 4 °C in the dark - Analytical monitoring:
- yes
- Details on sampling:
- Range-finding Test:
Samples for chemical analysis were taken but as results from the Algal Inhibition Range-Finding Test (Envigo Study Number: CY39CW) were available and indicated that the degradant cyclohexanone was stable for a period of 72 hours, it was considered unnecessary to have them analyzed.
Definitive Test
Samples were taken from the control and the 100 mg/L test group from the bulk test preparation at 0 hours and from the pooled replicates at 48 hours for quantitative analysis. All samples were stored frozen prior to analysis. Duplicate sets of samples were taken on each occasion and stored frozen for further analysis if necessary. - Vehicle:
- no
- Details on test solutions:
- Range-finding Test
A nominal amount of test item (200 mg) was dissolved in test water with the aid of magnetic stirring for 24 hours to give the 100 mg/L test concentration from which a series of dilutions was made to give further test concentrations of 0.10, 1.0 and 10 mg/L.
Each prepared concentration was inverted several times to ensure adequate mixing and homogeneity.
Definitive Test
A nominal amount of test item (200 mg) was dissolved in 2 liters of test water with the aid of magnetic stirring for 24 hours to give the 100 mg/L test concentration.
The prepared concentration was inverted several times to ensure adequate mixing and homogeneity. - Test organisms (species):
- Daphnia magna
- Details on test organisms:
- The test was carried out using first instar Daphnia magna derived from in-house laboratory cultures.
Adult daphnids were maintained in 150 mL glass beakers containing 100 mL Elendt M7 medium in a temperature controlled room maintaining the water temperature at 18 to 22 °C. The lighting cycle was controlled to give a 16 hours light and 8 hours darkness cycle with 20 minute dawn and dusk transition periods. Each culture was fed daily with a mixture of algal suspension (Desmodesmus subspicatus) and Tetramin® flake food suspension. Culture conditions ensured that reproduction was by parthenogenesis. Gravid adults were isolated the day before initiation of the test, such that the young daphnids produced overnight were less than 24 hours old. These young were removed from the cultures and used for testing. The diet and diluent water are considered not to contain any contaminant that would affect the integrity or outcome of the study. - Test type:
- static
- Water media type:
- freshwater
- Limit test:
- yes
- Total exposure duration:
- 48 h
- Test temperature:
- Temperature was maintained at 21 °C to 22 °C throughout the test,
- pH:
- 7.5 - 7.9
There were no treatment related differences for pH - Dissolved oxygen:
- 8.2 - 8.6 mg O2/L
There were no treatment related differences for oxygen concentration. - Nominal and measured concentrations:
- Range-finding Test
Nominal test concentrations of 0.10, 1.0, 10 and 100 mg/L.
Definitive Test
Nominal concentration: 100 mg/L
Analysis of the test preparation at 0 hours (see Annex 5) showed a measured cyclohexanone concentration of 38 mg/L. Analysis of the test preparation at 48 hours showed a measured cyclohexanone concentration of 32 mg/L (84% of its starting concentration). - Details on test conditions:
- Range-finding Test
In the range-finding test five daphnids were placed in each test and control vessel and maintained in a temperature controlled room maintaining the water temperature at 18 to 22 °C with a maximum deviation of ±1 °C and a photoperiod of 16 hours light and 8 hours darkness for a period of 48 hours with 20 minute dawn and dusk transition periods. Two replicate test and control vessels were prepared. Each 150 mL test and control vessel contained 100 mL of test media and was covered to reduce evaporation. After 24 and 48 hours the number of immobilized daphnids were recorded.
Definitive Test
Based on the results of the range-finding test a "Limit test" was conducted at a concentration of 100 mg/L to confirm that at the maximum concentration given in the OECD/EC Test Guidelines, no immobilization or adverse reactions to exposure were observed.
As in the range-finding test 150 mL glass beakers containing approximately 100 mL of test preparation were used. At the start of the test five daphnids were placed in each test and control vessel at random, containing the test preparations. Four replicate test and control vessels were prepared. The test vessels were then covered to reduce evaporation and maintained in a temperature controlled room maintaining the water temperature at 18 to 22 °C with a maximum deviation of ±1 °C and a photoperiod of 16 hours light (between 200 and 1200 Lux) and 8 hours darkness with 20 minute dawn and dusk transition periods. The daphnids were not individually identified, received no food during exposure and the test vessels were not aerated.
The control group was maintained under identical conditions but not exposed to the test item.
The test preparations were not renewed during the exposure period. - Reference substance (positive control):
- yes
- Remarks:
- Potassium Dichromate
- Duration:
- 48 h
- Dose descriptor:
- EC50
- Effect conc.:
- > 100 mg/L
- Nominal / measured:
- nominal
- Conc. based on:
- test mat.
- Basis for effect:
- mobility
- Duration:
- 48 h
- Dose descriptor:
- EC50
- Effect conc.:
- > 34.6 mg/L
- Nominal / measured:
- meas. (geom. mean)
- Conc. based on:
- other: cyclohexanone
- Basis for effect:
- mobility
- Remarks on result:
- other: based on hydrolysis product
- Duration:
- 48 h
- Dose descriptor:
- EC50
- Effect conc.:
- > 68.4 mg/L
- Nominal / measured:
- estimated
- Conc. based on:
- other: 2-[(2-hydroxyethyl)amino]ethyl 2-methylacrylate
- Basis for effect:
- mobility
- Remarks on result:
- other: based on hydrolysis product
- Remarks:
- theoretical maximum
- Details on results:
- Range-finding Test
No immobilization was observed throughout the test.
A sub-lethal effect of exposure was observed in the test concentrations of 0.10 and 1.0 mg/L. This response was trapping at surface.
Based on this information, a single test concentration of four replicates, of 100 mg/L was selected for the definitive test. This experimental design conforms to a "Limit test" to confirm that at the maximum test concentration given in the OECD/EC Test Guidelines no immobilization or adverse reactions to exposure were observed.
Definitive Test
Verification of Test Concentrations
The test item was found to hydrolyze rapidly upon addition to water, forming two primary hydrolysis species soluble in solution; cyclohexanone and 2-[(2-hydroxyethyl)amino]ethyl 2-methylacrylate. Whilst cyclohexanone undergoes no further reaction in the presence of water, 2-[(2-hydroxyethyl)amino]ethyl 2-methylacrylate was found to undergo further molecular rearrangement to produce a secondary degradation product N,N-bis(2-hydroxyethyl)-2-methylacrylamide.
Despite extensive method development work having been conducted, suitable methods of chemical analysis could not be developed for the quantification of concentrations of either 2-[(2-hydroxyethyl)amino]ethyl 2-methylacrylate or N,N-bis(2-hydroxyethyl)-2-methylacrylamide in solution. As such, analysis of the test preparations was conducted for the concentration of the primary degradant cyclohexanone only.”
Analysis of the test preparation at 0 hours showed a measured cyclohexanone concentration of 38 mg/L. Analysis of the test preparation at 48 hours showed a measured cyclohexanone concentration of 32 mg/L (84% of its starting concentration).
Given that toxicity cannot be attributed to any single degradant or combination of degradants, in accordance with the OECD Guidance Document on Aquatic Testing of Difficult Substances and Mixtures (OECD 2000), it was considered appropriate to calculate the results based on the nominal concentrations of the parent test item.
Immobilization Data
There was no immobilization in 20 daphnids exposed to a nominal test concentration of 100 mg/L for a period of 48 hours
The No Observed Effect Concentration after 24 and 48 hours exposure was 100 mg/L.
It was considered unnecessary and unrealistic to test at concentrations in excess of 100 mg/L.
Sub-Lethal Effects
No sub-lethal effects of exposure were observed throughout the test.
Validation Criteria
The test was considered to be valid given that none of the control daphnids showed immobilization or other signs of disease or stress and that the oxygen concentration at the end of the test was equal to or greater than 3 mg/L in the control and test vessels.
Observations on Test Item Solubility
At the start and throughout the test all control and test solutions were observed to be clear colorless solutions. - Results with reference substance (positive control):
- A positive control (Envigo study number LK67NP) used potassium dichromate as the reference item at concentrations of 0.32, 0.56, 1.0, 1.8 and 3.2 mg/L.
Exposure conditions for the positive control were similar to those in the definitive test.
Analysis of the immobilization data was carried out using the Binomial Distribution method at 24 hours and the Trimmed Spearman-Karber method at 48 hours. All statistical analysis was carried out using the ToxRat Professional computer software package with results based on the nominal test concentrations and gave the following results:
At 24 hours
EC50 mg/L: 0.79
95% Confidence Limits (mg/L): 0.73 - 0.86
NOEC (mg/L): 0.56
LOEC (mg/L): 1.0
At 48 hours
EC50 mg/L: 0.75
95% Confidence Limits (mg/L): 0.56 - 1.0
NOEC (mg/L): 0.56
LOEC (mg/L): 1.0
The NOEC is based upon equal to or less than 10% immobilization at this concentration.
The results from the positive control with potassium dichromate were within the normal range for this reference item. - Validity criteria fulfilled:
- yes
- Conclusions:
- From the results an EC50 value was calculated that is >100 mg/L (nominal). This is equal to a geometric mean measured concentration of 34.6 mg/L cyclohexanone. Initial concentration cyclohexanone was 37.7 mg/L, which is similar to the theoretical maximum amount of 38.7 mg/L that can be formed when 100 mg/L parent substance degrades.
From these results it can be shown that the parent substance was fully hydrolyzed at test start and test animals were exposed to cyclohexanone and 2-[(2-hydroxyethyl)amino]ethyl 2-methylacrylate.
100 mg/L parent substance is equal to 68.4 mg/L 2-[(2-hydroxyethyl)amino]ethyl 2-methylacrylate. - Executive summary:
Introduction
A study was performed to assess the acute toxicity of the test item to Daphnia magna. The method followed was designed to be compatible with the OECD Guidelines for Testing of Chemicals (April 2004) No 202, "Daphnia sp., Acute Immobilisation Test" referenced as Method C.2 of Commission Regulation (EC) No. 440/2008.
Methods
Following a preliminary range-finding test, 20 daphnids (4 replicates of 5 animals) were exposed to an aqueous solution of the test item at a nominal concentration of 100 mg/L for 48 hours at a temperature of 21 °C to 22 °C under static test conditions.
Immobilization and any adverse reactions to exposure were recorded after 24 and 48 hours.
Results
The test item was found to hydrolyze rapidly upon addition to water, forming two primary hydrolysis species soluble in solution; cyclohexanone and 2-[(2-hydroxyethyl)amino]ethyl 2-methylacrylate. Whilst cyclohexanone undergoes no further reaction in the presence of water, 2-[(2-hydroxyethyl)amino]ethyl 2-methylacrylate was found to undergo further molecular rearrangement to produce a secondary degradation product N,N-bis(2-hydroxyethyl)-2-methylacrylamide.
Despite extensive method development work having been conducted, suitable methods of chemical analysis could not be developed for the quantification of concentrations of either 2-[(2-hydroxyethyl)amino]ethyl 2-methylacrylate or N,N-bis(2-hydroxyethyl)-2-methylacrylamide in solution. As such, analysis of the test preparations was conducted for the concentration of the primary degradant cyclohexanone only.
Analysis of the test preparation at 0 hours showed a measured cyclohexanone concentration of 38 mg/L. Analysis of the test preparation at 48 hours showed a measured cyclohexanone concentration of 32 mg/L (84% of its starting concentration).
Given that toxicity cannot be attributed to any single degradant or combination of degradants, in accordance with the OECD Guidance Document on Aquatic Testing of Difficult Substances and Mixtures (OECD 2000), it was considered appropriate to calculate the results based on the nominal concentrations of the parent test item.
Exposure of Daphnia magna to the test item gave EC50 values of greater than 100 mg/L. The No Observed Effect Concentration (NOEC) was 100 mg/L.
Reference
Cumulative Immobilization Data and Observations in the Range-finding Test
Nominal Concentration |
Observations (Initial Population: 5 Per Replicate) |
|||||||
24 Hours |
48 Hours |
|||||||
Cumulative Immobilized Daphnia |
Observations |
Cumulative Immobilized Daphnia |
Observations |
|||||
R1 |
R2 |
R1 |
R2 |
R1 |
R2 |
R1 |
R2 |
|
Control |
0 |
0 |
5N |
5 N |
0 |
0 |
5 N |
5 N |
0.10 |
0 |
0 |
4 N 1T |
5 N |
0 |
0 |
5 N |
5 N |
1.0 |
0 |
0 |
5 N |
4 N 1 T |
0 |
0 |
5 N |
4 N 1 T |
10 |
0 |
0 |
5 N |
5 N |
0 |
0 |
5 N |
5 N |
100 |
0 |
0 |
5 N |
5 N |
0 |
0 |
5 N |
5 N |
R = Replicate
N = Normal
T = Trapped at surface
Cumulative Immobilization Data and Observations in the Definitive Test
Nominal Concentration |
24 Hours |
|||||||||
Cumulative Immobilized Daphnia |
Observations |
|||||||||
R1 |
R2 |
R3 |
R4 |
Total |
% |
R1 |
R2 |
R3 |
R4 |
|
Control |
0 |
0 |
0 |
0 |
0 |
0 |
5N |
5 N |
5 N |
5 N |
100 |
0 |
0 |
0 |
0 |
0 |
0 |
5 N |
5 N |
5 N |
5 N |
|
||||||||||
Nominal Concentration |
48 Hours |
|||||||||
Cumulative Immobilized Daphnia |
Observations |
|||||||||
R1 |
R2 |
R3 |
R4 |
Total |
% |
R1 |
R2 |
R3 |
R4 |
|
Control |
0 |
0 |
0 |
0 |
0 |
0 |
5 N |
5 N |
5 N |
5 N |
100 |
0 |
0 |
0 |
0 |
0 |
0 |
5 N |
5 N |
5 N |
5 N |
R = Replicate
N = Normal
Water Quality Measurements
Nominal Concentration |
0 Hours |
24 Hours |
48 Hours |
|||||
pH |
mg O2/L |
Temperature |
Temperature |
pH |
mg O2/L |
Temperature |
||
Control |
R1 |
7.5 |
8.2 |
22 |
21 |
7.9 |
8.9 |
21 |
100 |
R1 |
7.5 |
8.2 |
22 |
21 |
7.9 |
8.6 |
21 |
R = Replicate
Description of key information
The acute toxicity of 2 -(1 -oxa-4 -azaspiro[4.5]dec-4 -yl)ethyl methacrylate to invertebrates was determined in an OECD 202 study. In a limit test with 100 mg/L parent substance no effects were found. From this result an EC50value was calculated that is >100 mg/L (nominal). This is equal to a geometric mean measured concentration of 34.6 mg/L cyclohexanone (CAS 108 -94 -1). Initial concentration cyclohexanone was 37.7 mg/L, which is similar to the theoretical maximum amount of 38.7 mg/L that can be formed when 100 mg/L parent substance degrades.
From these results it can be shown that the parent substance was fully hydrolyzed at test start and test animals were exposed to cyclohexanone and 2-[(2-hydroxyethyl)amino]ethyl 2-methylacrylate (CAS 51706 -72 -0).
100 mg/L parent substance is equal to 68.4 mg/L 2-[(2-hydroxyethyl)amino]ethyl 2-methylacrylate.
This is in line with the estimated endpoints in EPIwin:
CAS 108 -94 -1: EC50 = 257 mg/L (neutral organics class)
CAS 51706 -72 -0: EC50 = 87 mg/L (aliphatic amines class)
CAS 45011 -26 -5: EC50 = 579 mg/L (acrylamides class)
Key value for chemical safety assessment
Additional information
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.