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EC number: - | CAS number: -
- 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:
- (Q)SAR
- Adequacy of study:
- key study
- Study period:
- 14 May 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® High-Accuracy-Quantitative Structure-Activity Relationship (HA-QSAR) based on a holistic approach for predicting physicochemical and ecotoxicological endpoints: Short-term toxicity to Daphnia (immobilisation)
2. MODEL (incl. version number)
iSafeRat® holistic HA-QSAR v1.9
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
SMILES: O=CCCCC/C=C1CCCC/1
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 ACUTE TOXICITY TO DAPHNIDS (48-HOUR EC50) was determined using iSafeRat® daphEC50, a validated QSAR model for the Mechanism of Action (MechoA) in question (MechoA 3.1, i.e. hard electrophile) (Bauer et al., 2018). 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. 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). The QSAR model is based on validated data for a training set of 5 chemicals derived from 48-hour test on daphnids.
- GLP compliance:
- no
- Remarks:
- QSAR model
- Specific details on test material used for the study:
- - log KOW: 4.18 (Phytosafe, 2013)
- Water Solubility: 17.6 mg/L (KREATiS, 2020) - 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.:
- 0.76 mg/L
- Nominal / measured:
- meas. (not specified)
- Conc. based on:
- test mat.
- Basis for effect:
- mobility
- Remarks on result:
- other: 95% confidence interval (α = 0.05): 0.53 – 1.1 mg/L
- Details on results:
- 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 0.76 mg/L. - Results with reference substance (positive control):
- not applicable
- Reported statistics and error estimates:
- 95% confidence interval (α = 0.05): 0.53 – 1.1 mg/L
- 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 0.76 mg/L.
95% confidence interval (α = 0.05): 0.53 - 1.1 mg/L. - Executive summary:
A Quantitative Structure-Activity Relationship (QSAR) model was used to calculate the ACUTE TOXICITY TO DAPHNIDS (48-HOUR EC50) of the test item. 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 ACUTE TOXICITY TO DAPHNIDS (48-HOUR EC50) was determined using iSafeRat® daphEC50, a validated QSAR model for the Mechanism of Action (MechoA) in question (MechoA 3.1, i.e. hard electrophile reactivity) (Bauer et al., 2018). The QSAR model is based on validated data for a training set of 5 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 48h-EC50 of the test item to daphnids was predicted as 0.76 mg/L.
95% confidence interval (α = 0.05): 0.53 - 1.1 mg/L.
- Endpoint:
- short-term toxicity to aquatic invertebrates
- Type of information:
- experimental study
- Adequacy of study:
- disregarded due to major methodological deficiencies
- Study period:
- From May 21, 2013 to May 28, 2013
- Reliability:
- 3 (not reliable)
- Rationale for reliability incl. deficiencies:
- significant methodological deficiencies
- Remarks:
- This study was performed according to OECD Guideline 202 with GLP certificate. All validity criteria were fulfilled. However, this study is not reliable due to high concentration of solvent used. Indeed, a large quantity of acetone was used as solvent in this study. Because of the potential for interaction with the test chemical resulting in an altered response in the test, solvent use should be restricted to situations where no other acceptable method of test solution preparation is available. The use of solvent is not the best method at the time being. In addition, the concentration/quantity of solvent used in the treatment solutions was 5 mL/L , corresponding to 3.95 g/L (with a density of 0.79), which is 50 times higher than the recommended maximum level of solvent (below 0.1 mL/L; OECD No. 23) and represent almost half of the EC50 of acetone (which was reported in the ECHA disseminated dossier at 8.8 g/L). Acetone is suspected to have affected the definitive results. Some solvent/substance interactions may have occurred in this study with this high concentration of acetone.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)
- Version / remarks:
- April 2004
- Deviations:
- yes
- Remarks:
- Solvent was used, which is not the best method existing at the time being.
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Inspection date on 14 June 2012 / GLP certificate signed on 10 January 2013
- Specific details on test material used for the study:
- - Storage condition: Room temperature protected from direct sun light
- Analytical monitoring:
- yes
- Details on sampling:
- The test item concentrations were measured before and after each renewal/adjustment.
- Vehicle:
- yes
- Remarks:
- acetone
- Details on test solutions:
- PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Method: The treatment solutions were prepared in acetone. Information concerning the preparation of the test item treatments is given in Table 6.1.1/1 in "Any other information on materials and methods incl. tables".
- Controls: water controls (the control tubes received 10 mL of M4 mineral medium) and solvent control (another set of 4 replicate tubes received 0.05 mL of acetone alone so as to ascertain that the vector had no adverse effects towards daphnids.
- Chemical name of vehicle (organic solvent, emulsifier or dispersant): acetone
- Concentration of vehicle in test medium (stock solution and final test solution(s) or suspension(s) including control(s)): 5 mL/L
- Evidence of undissolved material (e.g. precipitate, surface film, etc.): not reported - Test organisms (species):
- Daphnia magna
- Details on test organisms:
- TEST ORGANISM
- Strain/clone: Daphnia magna
- Source: received from a commercial breeder. These organisms were regularly sub-cultured at the Phytosafe site and fed with living cells of the green algae.
- Age of parental stock (mean and range, SD): Young daphnids produced within 24 hours were used for the tests.
- Feeding during test: Daphnids were not fed during the exposure period.
- Test type:
- semi-static
- Water media type:
- freshwater
- Remarks:
- M4 mineral medium
- Limit test:
- no
- Total exposure duration:
- 48 h
- Hardness:
- 64.8 mg/L of NaHCO3 in the reconstituted water.
- Test temperature:
- The temperature conditions were checked to be 20°C kept constant at +/- 1°C for both the range-finding test and the definitive test.
- pH:
- 7.5 to 8.1. Both the initial and the final values for pH were silimar to the controls for every test item treatments.
- Dissolved oxygen:
- 80.2 to 87.3 %. In every case the final oxygen concentration represented more than 80% of the saturation level.
- Salinity:
- Not applicable
- Nominal and measured concentrations:
- - Nominal treatment concentrations: 1.0, 2.1, 4.1, 8.2 and 16.4 mg/L.
- Measured concentrations: See table 6.1.1/2 in "Any other information on results incl. tables".
The initial concentrations did not deviate by more than 7% from the nominal values. After 24 hours of testing the measured concentrations were decreased down to 76-88% of the nominal values and the daphnids were transferred into newly prepared test tubes. At the end of test, the measured concentrations represented 42-81% of the nominal values. Based on mean measured concentrations over each successive period, and duration of each successive period, mean exposure concentrations were calculated as 0.8 - 1.6 - 3.5 - 7.1 and 15.0 mg/L. - Details on test conditions:
- TEST SYSTEM
- Test vessel: 15 mL capacity glass tubes
- Type (delete if not applicable): The tubes were maintained at dark in a climatic chamber, and were tightly capped during the exposure period so as to avoid volatilization of the test item. The controls were conducted accordingly.
- Material, size, headspace, fill volume: filled with 10 mL of M4 mineral medium
- Renewal rate of test solution (frequency/flow rate): semi-static methodology. The daphnids were transferred into newly prepared test tubes after 24 hours of exposure for the test item treatments, the water controls and the solvent controls.
- No. of organisms per vessel: 5 daphnids per replicate unit
- No. of vessels per concentration (replicates): 4 replicate units
- No. of vessels per control (replicates): 4 replicate units
- No. of vessels per vehicle control (replicates): 4 replicate units
TEST MEDIUM / WATER PARAMETERS
The M4 mineral medium was freshly reconstituted from mineral stock solutions.
EFFECT PARAMETERS MEASURED (with observation intervals if applicable) : Each test tube was checked for immobilized daphnids 24 and 48 hours after the start of the test. Any abnormal behavior or appearance, if any, was reported.
VEHICLE CONTROL PERFORMED: yes
RANGE-FINDING STUDY
- Test concentrations: 0.04 - 0.20 - 1.0 - 5.1 and 25.3 mg/L
- Results used to determine the conditions for the definitive study: No immobilization was observed throughout the test period for the water control and the solvent control. That was also the case for both the 0.04 and 1.0 mg/L test item treatments. At 0.20 mg/L one daphnid died on day 2 but the phenomenon was not confirmed at 1.0 mg/L and was not taken as a treatment induced effect. All the daphnids were immobilized after 24 hours of testing at 25.3 mg/L. The 5.1 mg/L test item treatment gave intermediate results. - Reference substance (positive control):
- yes
- Remarks:
- Potassium dichromate
- Key result
- Duration:
- 48 h
- Dose descriptor:
- EC50
- Effect conc.:
- 2.4 mg/L
- Nominal / measured:
- meas. (geom. mean)
- Conc. based on:
- test mat.
- Basis for effect:
- mobility
- Remarks on result:
- other: 95% confidence interval : 1.3 - 4.6 mg/L
- Duration:
- 48 h
- Dose descriptor:
- NOEC
- Effect conc.:
- 1.6 mg/L
- Nominal / measured:
- meas. (geom. 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".
- Results with reference substance (positive control):
- - Results with reference substance valid?
Yes
- ECx: 24h-EC50 for Potassium dichromate fell within 0.6 - 2.1 mg/L. Calculation gave 1.34 mg/L as the measured value. - Validity criteria fulfilled:
- yes
- Remarks:
- Immobilization was less than 10% in the controls; the dissolved oxygen concentration exceeded 3 mg/L in the controls and every test item treatment; the 24h-EC50 for potassium dichromate was between 0.6 and 2.1 mg/L.
- Conclusions:
- The 48h-EC50 value was determined at 2.4 mg/L, with a 95% CI of 1.3 - 4.6 mg/L, based on geometric mean measured concentrations.
Even if all validity criteria were fulfilled, this study is not reliable due to high concentration of solvent used. - Executive summary:
This study was performed according to OECD Guideline 202 with GLP statement, to assess the acute toxicity of the test substance to aquatic invertebrates Daphnia magna.
Following a preliminary range-finding study, 5 daphnids per replicate unit (4 replicate units per treatment) were exposed to the test item (prepared with acetone as solvent) at nominal concentrations of 1.0 - 2.1 - 4.1 - 8.2 and 16.4 mg/L, corresponding to geometric mean measured concentrations of 0.8 - 1.6 - 3.5 - 7.1 and 15.0 mg/L, for 48 hours under semi-static test conditions. The number of immobilised Daphnia was recorded after 24 and 48 hours.
Based on geometric mean measured concentrations, the 48 hour EC50 for the test item to Daphnia magna was 2.4 mg/L with 95% confidence limits of 1.3 - 4.6 mg/L. The highest tested concentration without observed effect was 1.6 mg/L.
Even if all validity criteria were fulfilled, this study is not reliable due to high concentration of solvent used. Indeed, a large quantity of acetone was used as solvent in this study. Because of the potential for interaction with the test chemical resulting in an altered response in the test, solvent use should be restricted to situations where no other acceptable method of test solution preparation is available. The use of solvent is not the best method at the time being. In addition, the concentration/quantity of solvent used in the treatment solutions was 5 mL/L , corresponding to 3.95 g/L (with a density of 0.79), which is 50 times higher than the recommended maximum level of solvent (below 0.1 mL/L; OECD No. 23) and represent almost half of the EC50 of acetone (which was reported in the ECHA disseminated dossier at 8.8 g/L). Acetone is suspected to have affected the definitive results. Some solvent/substance interactions may have occurred in this study with this high concentration of acetone.
Referenceopen allclose all
Applicability Domain
Descriptor domain
The Subcooled Liquid Water Solubility value (17.6 mg/L or -3.974 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 -5.15 to -0.080 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 iSafeRat® daphEC50 model 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 aldehyde is expected to exert a MechoA 3.1 and can be taken into account by the model (Bauer et al., 2018).
Table 6.1.3/2 : Measured concentrations for the test substance (mg/L) throughout the test period
Nominal values |
Day 1 |
Day 2 |
||
New media |
Old media |
New media |
Old media |
|
1.0 mg/L 2.1 mg/L 4.1 mg/L 8.2 mg/L 16.4 mg/L |
1.03 2.09 4.40 7.88 16.37 |
0.78 1.58 3.60 7.02 13.74 |
1.08 2.12 4.14 8.15 17.09 |
0.44 0.87 2.21 5.79 13.30 |
Table 6.1.3/3 : Definitive test - % immobilized daphnids for the controls and the test item treatments
|
% immobilization after 24 hours |
% immobilization after 48 hours |
|||||||
Rep 1 |
Rep 2 |
Rep 3 |
Rep 4 |
Rep 1 |
Rep 2 |
Rep 3 |
Rep 4 |
||
Water control |
0 |
0 |
0 |
0 |
20 |
0 |
0 |
0 |
|
Solvent control |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Test substance |
0.8 mg/L 1.6 mg/L 3.5 mg/L 7.1 mg/L 15.0 mg/L |
0 20 20 40 60 |
0 0 40 20 40 |
0 20 20 40 60 |
0 0 20 20 60 |
0 40 80 100 100 |
0 40 60 100 100 |
0 40 80 80 100 |
0 0 80 80 100 |
Description of key information
iSafeRat® High-Accuracy-Quantitative Structure-Activity Relationship, KREATIS, 2020 :
48h-EC50 = 0.76 mg/L (95% confidence interval: 0.53 - 1.1 mg/L)
Key value for chemical safety assessment
Fresh water invertebrates
Fresh water invertebrates
- Effect concentration:
- 0.76 mg/L
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 (Phytosafe, 2013) was considered as not reliable and was disregarded due to major methodological deficiencies. Indeed, a large quantity of acetone was used as solvent in this study. Because of the potential for interaction with the test chemical resulting in an altered response in the test, solvent use should be restricted to situations where no other acceptable method of test solution preparation is available. The use of solvent is not the best method at the time being. In addition, the concentration/quantity of solvent used in the treatment solutions was 5 mL/L , corresponding to 3.95 g/L (with a density of 0.79), which is 50 times higher than the recommended maximum level of solvent (below 0.1 mL/L; OECD No. 23) and represent almost half of the EC50 of acetone (which was reported in the ECHA disseminated dossier at 8.8 g/L). Therefore, solvent/substance interactions may have occured in this study with this high concentration of acetone and the result cannot be considered fit for use.
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 3.1, i.e. hard electrophile reactivity) (Bauer et al., 2018). The QSAR model is based on validated data for a training set of 5 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 0.76 mg/L (95% CI: 0.53 - 1.1 mg/L).
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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