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EC number: 233-881-7 | CAS number: 10411-92-4
- 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
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:
- disregarded due to major methodological deficiencies
- Study period:
- From 04 February 2013 to 04 March 2013
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- significant methodological deficiencies
- Remarks:
- This study was performed according to OECD Guideline 202 and EU Method C.2 with GLP statement. All validity criteria were fulfilled. However, the measured concentration of the 100% v/v saturated solution used to prepare the different test concentrations was determined at 28 mg/L, which is well greater than the real water solubility value. The saturated solution was prepared by dispersing an amount of test substance is reconstituted water with the aid of propeller stirring for 24 hours. After 24 hours, the stirring was stopped and any undissolved test substance was removed by filtration to give the saturated solution. An hypothesis of this high measured concentration (28 mg/L) whould be that 24 hours of stirring is not sufficient to dissolve this test substance and even if clear colorless solutions were reported, stable emulsions are suspected to be formed, which can explain possible physical effects. Due to this significant methodological deficiencies (tested concentrations greater than the water solubility value), this study is not reliable.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method C.2 (Acute Toxicity for Daphnia)
- Deviations:
- no
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- 2012-11-30
- Analytical monitoring:
- yes
- Details on sampling:
- Water samples were taken from the control and each test group (replicates R1 – R4 pooled) at 0 and 24 hours (old media) and from the control and each surviving test group at 24 (fresh media) and 48 hours (old media) for quantitative analysis. Samples were stored at approximately -20 °C prior to analysis.
- Vehicle:
- no
- Details on test solutions:
- Preliminary solubility work conducted indicated that the test item was practically insoluble in water using traditional methods of preparation e.g. ultrasonication and high shear mixing.
Based on this information, a media preparation trial was conducted in order to determine the solubility of the test item under test conditions. The test item was prepared using a rapid stir saturated solution method of preparation, stirred for a period of 24 hours prior to the removal of any undissolved test item by filtration through a 0.2 μm Sartorius Sartopore filter (first approximate 2 liters discarded) to give a nominal test concentration of approximately 32 mg/L.
PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
An amount of test item (1100 mg) was dispersed in 11 liters of reconstituted water with the aid of propeller stirring at approximately 1500 rpm for 24 hours. After 24 hours the stirring was stopped and any undissolved test item was removed by filtration through a 0.2 μm Sartorius Sartopore filter (first approximate 2 liters discarded in order to pre-condition the filter) to give a 100% v/v saturated solution with a mean measured concentration of 28 mg/L. A series of dilutions was made from the saturated solution to give further test concentrations of 56, 32, 18 and 10% v/v saturated solution (equivalent to mean measured test concentrations of 15, 8.7, 4.7 and 3.7 mg/L).
Each prepared concentration was inverted several times to ensure adequate mixing and homogeneity. - Test organisms (species):
- Daphnia magna
- Details on test organisms:
- TEST ORGANISM
- Common name: Daphnia magna
- Strain: no data
- Source: in-house laboratory cultures
- Age at study initiation (mean and range, SD): 1st instar (less than 24 hours old)
- Weight at study initiation (mean and range, SD): no data
- Length at study initiation (length definition, mean, range and SD): no data
- Valve height at study initiation, for shell deposition study (mean and range, SD): no data
- Peripheral shell growth removed prior to test initiation: no data
- Method of breeding: no data
- Feeding during test: no
ACCLIMATION
Adult Daphnia were maintained in 150 mL glass beakers containing Elendt M7 medium in a temperature controlled room at approximately 20 °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. - Test type:
- semi-static
- Water media type:
- freshwater
- Limit test:
- no
- Total exposure duration:
- 48 h
- Remarks on exposure duration:
- none
- Post exposure observation period:
- None
- Hardness:
- 250 mg/L as CaCO3
- Test temperature:
- 20 to 21°C
- pH:
- 7.8 to 8.1
- Dissolved oxygen:
- 8.7 to 9.5 mg O2/L (96 to 106% of Air Saturation Value)
- Salinity:
- Not applicable
- Nominal and measured concentrations:
- - Nominal concentrations: Control, 10, 18, 32, 56 and 100% v/v saturation solution
- Measured concentrations: See table 6.1.3/1 and 6.1.3/2 in "Any other information on results incl. tables". - Details on test conditions:
- TEST SYSTEM
- Test vessel: 100 mL ground glass stoppered conical flasks
- Aeration: no
- Renewal rate of test solution (frequency/flow rate): daily renewal of the test preparations
- No. of organisms per vessel: 5
- No. of vessels per concentration (replicates): 4
- No. of vessels per control (replicates): 4
- No. of vessels per vehicle control (replicates): not applicable
TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: Reconstituted water
- Stock Solutions:
a) CaCl2.2H2O = 11.76 g/L;
b) MgSO4.7H2O = 4.93 g/L;
c) NaHCO3 = 2.59 g/L;
d) KCl = 0.23 g/L.
- Preparation: An aliquot (25 mL) of each of solutions (a) to d)) was added to each liter (final volume) of deionized water with a conductivity of <5 μS cm-1. The reconstituted water had a pH of 7.8 ± 0.2 and was aerated until the dissolved oxygen concentration was approximately air-saturation value. The reconstituted water had an approximate theoretical total hardness of 250 mg/L as CaCO3.
OTHER TEST CONDITIONS
- Adjustment of pH: no
- Photoperiod: 16h light and 8h darkness with 20 minute dawn and dusk transition periods
- Light intensity: 638 to 663 lux
EFFECT PARAMETERS MEASURED (with observation intervals if applicable) : Any immobilization or adverse reactions to exposure were recorded at 24 and 48 hours after the start of exposure. The criterion of effect used was that Daphnia were considered to be immobilized if they were unable to swim for approximately 15 seconds after gentle agitation.
TEST CONCENTRATIONS
- Range finding study: yes (0.10, 1.0, 10 and 100% v/v saturation solution).
- Results used to determine the conditions for the definitive study: No immobilization was observed at the test concentrations of 0.10, 1.0 and 10% v/v saturated solution. However, 100% immobilization was observed at 100% v/v saturated solution. Based on this information test concentrations of 10, 18, 32, 56 and 100% v/v saturated solution were selected for the definitive test. Chemical analysis of the 10 and 100% v/v saturated solution test preparations at 0 hours showed measured test concentrations of 3.0 and 27 mg/L respectively were obtained. A decline in measured test concentration was observed at 48 hours to 1.9 and 19 mg/L for the 10 and 100% v/v saturated solution test preparations respectively. These results indicated that the test item was possibly unstable under test conditions and therefore it was considered appropriate to perform the definitive test using semi-static conditions in order to try and maintain near nominal test concentrations. - Reference substance (positive control):
- yes
- Remarks:
- Potassium dichromate
- Key result
- Duration:
- 48 h
- Dose descriptor:
- EC50
- Effect conc.:
- 5.3 mg/L
- Nominal / measured:
- meas. (arithm. mean)
- Conc. based on:
- test mat.
- Basis for effect:
- mobility
- Remarks on result:
- other: 95% CL: 4.8-6.5 mg/L
- Duration:
- 48 h
- Dose descriptor:
- other: The highest concentration without observed effect
- Effect conc.:
- 3.7 mg/L
- Nominal / measured:
- meas. (arithm. mean)
- Conc. based on:
- test mat.
- Basis for effect:
- mobility
- Details on results:
- See table 6.1.3/3 in "Any other information on results incl. tables".
- Behavioural abnormalities: not reported
- Observations on body length and weight: not reported
- Other biological observations: not reported
- Mortality of control: none (0%)
- Other adverse effects control: none
- Abnormal responses: not reported
- Any observations (e.g. precipitation) that might cause a difference between measured and nominal values: none
- Effect concentrations exceeding solubility of substance in test medium: No. Throughout the duration of the test all control and test preparations were observed to be clear colorless solutions. - Results with reference substance (positive control):
- - Results with reference substance valid? yes
- 24h EC50 = 0.75 mg/L (95% CL: 0.56-1.0 mg/L); 24h NOEC = 0.56 mg/L.
- 48h EC50 = 0.45 mg/L (95% CL: 0.42-0.48 mg/L); 48h NOEC = 0.32 mg/L. - Reported statistics and error estimates:
- The slope and the standard error of the response curve at 48 hours was 12 (SE = 3.3).
- Validity criteria fulfilled:
- yes
- Conclusions:
- The 48h-EC50 based on mean measured test concentrations was 5.3 mg/L (95% confidence limits: 4.8 – 6.5 mg/L). This value is greater than the real water solubility value.
- Executive summary:
This study was performed, according to OECD Guideline 202 and EU Method C.2 with GLP statement, to assess the acute toxicity of the substance to Daphnia magna.
Pre-study solubility work conducted indicated that it was not possible to obtain a testable solution of the test item using traditional methods of preparation e.g. ultrasonication and high shear mixing.
A pre-study media preparation trial indicated that a dissolved test item concentration of approximately 32 mg/L was obtained from a saturated solution method of preparation indicating this to be the limit of water solubility of this item under test conditions.
Following a preliminary range-finding tests, twenty daphnids (4 replicates of 5 animals) were exposed to an aqueous solution of the substance at mean measured concentrations of 3.7, 4.7, 8.7, 15 and 28 mg/L for 48 hours at a temperature of 20 °C to 21 °C under semi-static test conditions. The test item solution was prepared by stirring an excess (100 mg/L) of test item in test medium using a propeller stirrer at approximately 1500 rpm for 24 hours. After the stirring period any undissolved test item was removed by filtration (0.2 μm Sartorius Sartopore filter, first approximate 2 liters discarded in order to pre-condition the filter) to produce a 100% v/v saturated solution of the test item with a mean measured concentration of 28 mg/L. A series of dilutions was made from this saturated solution to further give test concentrations of 56, 32, 18 and 10% v/v saturated solution (equivalent to mean measured test concentrations of 15, 8.7, 4.7 and 3.7 mg/L). The number of immobilized Daphnia were recorded after 24 and 48 hours.
Due to the potentially volatile nature of the substance, the test was conducted in completely filled and sealed test vessels.
Exposure of Daphnia magna to the substance gave a 48-Hour EC50 value based on the mean measured test concentrations of 5.3 mg/L (95% confidence limits: 4.8 – 6.5 mg/L). The highest concentration without observed effect was 3.7 mg/L.
Even if all validity criteria were fulfilled, this study is not realiable due to significant methodological deficiencies (tested concentrations greater than the water solubility value). The measured concentration of the 100% v/v saturated solution used to prepare the different test concentrations was determined at 28 mg/L, which is well greater than the real water solubility value. The saturated solution was prepared by dispersing an amount of test substance is reconstituted water with the aid of propeller stirring for 24 hours. After 24 hours, the stirring was stopped and any undissolved test substance was removed by filtration to give the saturated solution. An hypothesis of this high measured concentration (28 mg/L) whould be that 24 hours of stirring is not sufficient to dissolve this test substance and even if clear colorless solutions were reported, stable emulsions are suspected to be formed, which can explain possible physical effects.
- Endpoint:
- short-term toxicity to aquatic invertebrates
- Type of information:
- (Q)SAR
- Adequacy of study:
- key study
- Study period:
- From March 20th, 2020 to March 23rd, 2020
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
- Justification for type of information:
- 1. SOFTWARE
iSafeRat® HA-QSAR toolbox v2.5
2. MODEL (incl. version number)
iSafeRat® daphEC50 v1.9
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CC(=O)O[C@@H]1CC[C@@H](CC1)C(C)(C)C
Input for the prediction: Subcooled Liquid Water Solubility (SLWS) of the test item. For liquids at 25°C, the SLWS is directly equal to the value of the Water Solubility of the test item. Water Solubility of the test item was predicted to be 4.16 mg/L or -4.678 in log10 (mol/L) at 25°C (KREATiS, 2020) using the measured log KOW value as the input. Log KOW of the test item was experimentally measured to be 4.8 at 25°C (Givaudan, 1996).
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF
5. APPLICABILITY DOMAIN
See attached QPRF
6. ADEQUACY OF THE RESULT
See attached QPRF - Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)
- Deviations:
- not applicable
- Remarks:
- QSAR model
- Principles of method if other than guideline:
- The purpose of this QSAR model is to accurately predict the acute toxicity to daphnids as would be expected in a laboratory experiment following OECD Guideline 202 and EC method C.2 for specific, named mechanisms of action. The model provides an in silico prediction for the 48-hour EC50 value that can effectively be used in place of an experimentally derived 48-hour EC50 value. The regression based method used to achieve this has been fully validated following the OECD recommendations (OECD, 2004).
- GLP compliance:
- no
- Remarks:
- QSAR model
- Specific details on test material used for the study:
- - log KOW = 4.8 (experimental study performed on a read-across substance, Givaudan, 1996)
- Water Solubility = 4.16 mg/L (KREATiS, 2020)
- Mechanism of action: MechoA 2.1: mono-/poly-esters whose hydrolysis products are narcotics (Bauer et al., 2018) - Analytical monitoring:
- no
- Details on sampling:
- not applicable
- Vehicle:
- no
- Details on test solutions:
- not applicable
- Test organisms (species):
- other: Daphnia magna, Daphnia pulex
- Details on test organisms:
- No difference in terms of toxic mechanism of action between invertebrate (or indeed other) aquatic species is expected. Any observed differences may be attributed to lifestyle related parameters (e.g. shell closing in molluscs) and relative duration of study versus bodysize rather than to a specific toxic mechanism causing species differences.
- Test type:
- other: QSAR model
- Water media type:
- freshwater
- Limit test:
- no
- Total exposure duration:
- 48 h
- Remarks on exposure duration:
- Results from a test duration of 48 hours only were used for daphnid species.
- Post exposure observation period:
- not applicable
- Hardness:
- The QSAR is based on data from studies performed at acceptable hardness to ensure control survival.
- Test temperature:
- The temperatures varied from approximately 20 to 23 °C depending on the species used to construct the algorithm. This small difference is not expected to contribute to the variability of the EC50 values found in experimental data.
- pH:
- Test results were taken from studies with measured pHs between 6 - 9.
- Dissolved oxygen:
- The model is based on data from studies performed at acceptable oxygen concentrations (generally >60%).
- Salinity:
- Not applicable
- Conductivity:
- Not applicable
- Nominal and measured concentrations:
- Studies were used only where sufficient evidence was presented to determine that the substance was stable under test conditions (i.e. maintained within ± 20 % of the nominal) or, if not, the result was based on measured concentrations as geometric mean.
- Details on test conditions:
- Preferentially results from semi-static studies were used. However, substances tested using a static design were accepted (preferably accompanied by analytical measurements over the study period). For suspected volatile substances only tests performed in closed vessels were accepted unless accompanying analytical monitoring proved such a design was not necessary.
- Reference substance (positive control):
- no
- Remarks:
- QSAR model
- Key result
- Duration:
- 48 h
- Dose descriptor:
- EC50
- Effect conc.:
- 4.2 mg/L
- Nominal / measured:
- meas. (not specified)
- Conc. based on:
- test mat.
- Basis for effect:
- mobility
- Remarks on result:
- other: 95%CL: 3.2 - 5.5 mg/L
- Remarks:
- The toxicity value is greater than the limit of solubility within the exposure period of the test.
- Details on results:
- The test item falls within the applicability domain of the model and can therefore be considered as a reliable prediction for ACUTE TOXICITY TO DAPHNIDS (48-HOUR EC50). Therefore, this endpoint value can be considered valid for use in risk assessment and classification and labelling.
The 48h-EC50 of the test item to daphnids was predicted as 4.2 mg/L. Therefore, the toxicity value is greater than the limit of solubility within the exposure period of the test. - Results with reference substance (positive control):
- not applicable
- Reported statistics and error estimates:
- 95% confidence interval (α = 0.05): 3.2 - 5.5 mg/L.
QSAR statistical parameters are given in the QMRF and the QPRF - Validity criteria fulfilled:
- yes
- Conclusions:
- The test item falls within the applicability domain of the model and was therefore reliably predicted for its acute toxicity (48h-EC50) to daphnids. Therefore, this endpoint value can be considered valid for use in risk assessment and classification and labelling.
The 48h-EC50 of the test item to daphnids was predicted as 4.2 mg/L. Therefore, the toxicity value is greater than the limit of solubility within the exposure period of the test.
95% confidence interval (α = 0.05): 3.2 – 5.5 mg/L. - Executive summary:
A Quantitative Structure-Activity Relationship (QSAR) model was used to calculate the acute toxicity of the test item to daphnid. This QSAR model has been validated to be compliant with the OECD recommendations for QSAR modeling (OECD, 2004a) and predicts the endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following the Guideline for Testing of Chemicals No. 202, "Daphnia sp., Acute Immobilisation Test" (OECD, 2004b), referenced as Method C.2 of Commission Regulation No. 440/2008 (European Commission, 2008). The criterion predicted was the EC50 (Median Effective Concentration), a statistically derived concentration which is expected to cause immobility in 50% of test animals within a period of 48 hours.
The immobility of the daphnids was determined using a validated QSAR model for the Mechanism of Action (MechoA) in question (MechoA 2.1, i.e. mono-/poly-esters whose hydrolysis products are narcotics) (Bauer et al., 2018). The QSAR model is based on validated data for a training set of 41 chemicals derived from 48-hour test on daphnids, for which the concentrations of the test item had been determined by chemical analyses over the test period.
The 48h-EC50 of the test item to daphnids was predicted as 4.2 mg/L. Therefore, the toxicity value is greater than the limit of solubility within the exposure period of the test.
95% confidence interval (α = 0.05): 3.2 – 5.5 mg/L.
Referenceopen allclose all
Table 6.1.3/1: Measured concentrations during the test
Time point (hours) |
Nominal concentrations (% v/v saturation solution) |
Measured concentrations (mg/L) |
% to initial concentrations |
0 - fresh |
Control 10 18 32 56 100 |
<LOQ 4.85 5.02 9.21 15.3 29.3 |
- |
24 - old |
Control 10 18 32 56 100 |
<LOQ 3.83 4.19 7.83 14.0 27.1 |
- 79 83 85 92 92 |
24 - fresh |
Control 10 18 32 |
<LOQ 3.17 5.19 8.92 |
- - - - |
48 - old |
Control 10 18 32 |
<LOQ 2.79 4.57 8.98 |
- 88 88 101 |
Table 6.1.3/2: Mean measured concentrations
Nominal concentrations (% v/v saturation solution) |
Mean measured concentrations (mg/L) |
Control 10 18 32 56 100 |
<LOQ 3.7 4.7 8.7 15 28 |
Table 6.1.3/3: Cumulative immobilization data in the definitive test
Mean measured concentrations (mg/L) |
Cumulative immobilized Daphnia (initial population: 5 per replicate) |
|||||||||||
24 hours |
48 hours |
|||||||||||
R1 |
R2 |
R3 |
R4 |
Total |
% |
R1 |
R2 |
R3 |
R4 |
Total |
% |
|
Control |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
3.7 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
1 |
0 |
1* |
5 |
4.7 |
0 |
2 |
0 |
0 |
2 |
10 |
0 |
2 |
2 |
1 |
5 |
25 |
8.7 |
4 |
4 |
3 |
3 |
14 |
70 |
5 |
5 |
5 |
5 |
20 |
100 |
15 |
5 |
5 |
5 |
5 |
20 |
100 |
5 |
5 |
5 |
5 |
20 |
100 |
28 |
5 |
5 |
5 |
5 |
20 |
100 |
5 |
5 |
5 |
5 |
20 |
100 |
* Single immobilized daphnid considered to be due to natural causes rather than a true toxic effect given that less than 10% immobilization occurred.
Applicability Domain of the model
Descriptor domain:
The Subcooled Liquid Water Solubility value (4.16 mg/L or -4.678 in log10 (mol/L)) given as the input to the iSafeRat® daphEC50 model falls within the descriptor domain of the model between a Subcooled Liquid Water Solubility of -4.79 to 0.93 in log10 (mol/L).
Structural fragment domain:
All chemical groups within the molecular structure are taken into account by the model.
Mechanistic domain:
Currently, the ecotoxicity module of the iSafeRat® Holistic HA-QSAR can reliably predict the aquatic toxicity for chemicals with the following mechanisms of action of toxicity (MechoA):
• non-polar narcosis (MechoA 1.1)
• polar narcosis of alkyl-/alkoxy-phenols (MechoA 1.2)
• polar narcosis of aliphatic amines (MechoA 1.2)
• cationic narcosis of quaternary ammoniums (MechoA 1.3)
• mono-/poly-esters whose hydrolysis products are narcotics (MechoA 2.1)
• hard electrophile reactivity (MechoA 3.1)
• RedOx cycling of primary thiols (MechoA 4.4)
• Proton release of carboxylic acids (MechoA 5.2)
The MechoA of molecules is predicted directly from the structure. The test item as an ester is expected to exert a MechoA 2.1 and can be taken into account by the model (Bauer et al., 2018).
See QMRF in "attached background material".
Description of key information
iSafeRat® HA-QSAR toolbox v2.5, KREATiS, 2020:
48h-EC50 > solubility limit
Key value for chemical safety assessment
Additional information
One experimental study and one QSAR prediction are available to assess the short-term toxicity of the registered substance to aquatic invertebrates.
The experimental study (Harlan, 2013), performed on the registered substance according to OECD Guideline 202 and EU Method C.2 with GLP statement was considered as not reliable and was disregarded due to major methodological deficiencies. Exposure of Daphnia magna to the test substance gave a 48h-EC50 value based on the mean measured test concentrations of 5.3 mg/L (95% CL: 4.8 - 6.5 mg/L). Even if all validity criteria were fulfilled, the measured concentration of the 100% v/v saturated solution used to prepare the different test concentrations was determined at 28 mg/L, which is well greater than the real water solubility value (determined at 4.16 mg/L (KREATiS, 2020)). The saturated solution was prepared by dispersing an amount of test substance is reconstituted water with the aid of propeller stirring for 24 hours. After 24 hours, the stirring was stopped and any undissolved test substance was removed by filtration to give the saturated solution. An hypothesis of this high measured concentration (28 mg/L) whould be that 24 hours of stirring is not sufficient to dissolve this test substance and even if clear colorless solutions were reported, stable emulsions are suspected to be formed, which can explain possible physical effects at this saturated solution and other tested concentrations.
The QSAR prediction (KREATiS, 2020) was considered as reliable. The QSAR model has been validated to be compliant with the OECD recommendations for QSAR modelling (OECD, 2004) and predicts the endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following OECD Guideline 202.The immobility of the daphnids was determined using a validated QSAR model for the Mechanism of Action (MechoA) in question (MechoA 2.1, i.e. mono-/poly-esters whose hydrolysis products are narcotics) (Bauer et al., 2018). The QSAR model is based on validated data for a training set of 41 chemicals derived from 48 -hour test on daphnids, for which the concentrations of the test item had been determined by chemical analyses over the test period. The test item falls within the applicability domain of the model and was therefore reliably predicted for its acute toxicity (48h-EC50) to daphnids. Therefore, this endpoint value can be considered valid for use in risk assessment and classification and labelling.
The 48-h EC50 of the registered substance to daphnids was predicted at 4.2 mg/L (95% CI: 3.2 - 5.5 mg/L). The toxicity value is greater than the limit of solubility (determined at 4.16 mg/L) within the exposure period of the test.
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.