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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:
- experimental study
- Adequacy of study:
- disregarded due to major methodological deficiencies
- Study period:
- From December 5, 2012 to December 10, 2012
- 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:
- Certificate signed on March 11, 2011.
- Specific details on test material used for the study:
- - Physical state: white crystalline powder
- Storage condition: Room temperature protected from direct sun light - Analytical monitoring:
- yes
- 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.
- Controls: Solvent control : a 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. see Table 6.1.3/1 in any other information - Test organisms (species):
- Daphnia magna
- Details on test organisms:
- TEST ORGANISM
- Strain/clone: Daphnia magna
- Source: received from a commercial breeder
- Age of parental stock (mean and range, SD): Young daphnids produced within 24 hours were used for the tests
- Test type:
- static
- Water media type:
- other: M4 mineral medium was freshly reconstituted from mineral stock solutions. The composition is presented in Appendix 3.
- Limit test:
- no
- Total exposure duration:
- 48 h
- Test temperature:
- 20 +/- 1°C
- pH:
- 7.7 - 9.1
- Dissolved oxygen:
- 84.3 - 102.4 %
- Nominal and measured concentrations:
- Definitive test: 0.19 - 0.34 - 0.60 - 1.10 and 2.00 mg/L based on analytically confirmed nominal concentrations
- Details on test conditions:
- TEST SYSTEM
- Test vessel: 15 mL capacity glass tubes
- Type (delete if not applicable): closed
- Material, size, headspace, fill volume: filled with 10 mL of M4 mineral medium
- Renewal rate of test solution (frequency/flow rate):
- 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
EFFECT PARAMETERS MEASURED (with observation intervals if applicable) : immobility
VEHICLE CONTROL PERFORMED: yes
RANGE-FINDING STUDY
- Test concentrations: 0.01 - 0.1 - 1.0 - 10.0 and 99.8 mg/L
- Results used to determine the conditions for the definitive study: No immobilization was observed for the 0.01, 0.1 and 1.0 mg/L test item treatments. All the daphnids were immobilized at 10.0 abd 99.8 mg/L. at the end of the test, 40% immobilization was observed in the 1.0 mg/L test item treatment. - Reference substance (positive control):
- yes
- Remarks:
- Potassium dichromate
- Key result
- Duration:
- 48 h
- Dose descriptor:
- EC50
- Effect conc.:
- 0.79 mg/L
- Nominal / measured:
- nominal
- Conc. based on:
- test mat.
- Basis for effect:
- mobility
- Remarks on result:
- other: 95% confidence interval : 0.42 - 1.47 mg/L ; analytically confirmed concentrations : recovery of the test item of 97.8 - 100.7 %.
- Duration:
- 48 h
- Dose descriptor:
- NOEC
- Effect conc.:
- 0.34 mg/L
- Nominal / measured:
- nominal
- Conc. based on:
- test mat.
- Basis for effect:
- mobility
- Remarks on result:
- other: analytically confirmed concentrations : recovery of the test item of 97.8 - 100.7 %.
- Details on results:
- - Mortality of control: No
- 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. - Reported statistics and error estimates:
- F values were compared to F(1,6) = 5.99 at the 5% confidence level. The NOEC was 1.10 mg/L on day 1 and 0.34 mg/L on day 2 of the test period.
- 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 0,79 mg/L, with a 95% CI of 0.42 - 1.47 mg/L, based on analytically confirmed nominal 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 to assess the acute toxicity of the test item to Daphnia magna. The method followed is the OECD Guideline No. 202.
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 concentrations of 0.19 - 0.34 - 0.60 - 1.10 and 2.00 mg/L (analytically confirmed nominal concentrations, recovery of the test item of 97.8 - 100.7 %) for 48 hours under static test conditions. The number of immobilised Daphnia was recorded after 24 and 48 hours.
The 48 hour EC50 for the test item to Daphnia magna based on nominal test concentrations was 0.79 mg/L and the 95% confidence interval was 0.42 - 1.47 mg/L. The highest concentration tested without observed effect was 0.34 mg/L.
Analysis of the test solutions at the end of the test showed the measured test concentrations to be in excess of the required 80% of nominal and so the results are based on nominal test concentrations only.
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.
- Endpoint:
- short-term toxicity to aquatic invertebrates
- Type of information:
- (Q)SAR
- Adequacy of study:
- key study
- Study period:
- October 1st, 2019
- 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® holistic HA-QSAR v1.8
2. MODEL (incl. version number)
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)
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CC1(C)C2(C3)C(C(C3(CCC)CC2)=O)CCC1
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)
- Principles of method if other than guideline:
- The immobility of the daphnids was determined using a validated QSAR model for the Mechanism of Action (MechoA) in question (MechoA 1.1, i.e. non-polar narcosis) (4). The QSAR model is based on validated data for a training set of 58 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.
- GLP compliance:
- no
- Specific details on test material used for the study:
- - Mechanism of action : MechoA 1.1: non-polar narcosis (Bauer et al., 2018)
- Melting point: 46.1°C (Phytosafe, 2012; EU Method A.1; DSC Method)
- Water solubility : 5.4 mg/L (Phytosafe, 2012; EU Method A.6; Column Elution Method) - Analytical monitoring:
- not required
- Details on sampling:
- not applicable
- Vehicle:
- no
- Details on test solutions:
- Not applicable
- Test organisms (species):
- Daphnia sp.
- Details on test organisms:
- Results from the following species were used in the regression: Daphnia magna, Daphnia pulex.
No difference in relationship between solubility and ecotoxicity 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
- Water media type:
- freshwater
- Limit test:
- no
- Total exposure duration:
- 48 h
- Post exposure observation period:
- Not applicable
- Hardness:
- Not applicable
- 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 dissolved oxygen concentration was more than 60% of the air-saturation value throughout the duration of the test. In exceptional cases where studies with oxygen concentrations lower than 60% were used, all aspects of the study were thoroughly evaluated in order to satisfy the evaluator that the effects found were not due to reduced oxygen concentration (i.e. the study would correctly receive a Klimisch score of 2 under the REACH Regulation (REACH, 2006).
- Salinity:
- Not applicable
- Conductivity:
- Not applicable
- Nominal and measured concentrations:
- Studies were used only where analytical measurements were made on the control and all relevant test concentrations whenever possible. Any exceptions (initial concentrations measured only or EC50 based on nominal values) were used only when sufficient justification for stability of the test item was determined.
When nominal concentrations from training set data were used, the concentrations of the test substance had been shown to be maintained to within 80% of the nominal concentrations throughout the duration of the study either using analytical verification or by application of a weight of evidence approach that such an assumption was justified. If the deviation from the nominal concentration was >20%, the results were based on the measured concentrations. - Details on test conditions:
- This QSAR model has been validated to be compliant with the OECD recommendations for QSAR modeling (OECD, 2004) 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", referenced as Method C.2 of Commission Regulation No. 440/2008.
The immobility of the daphnids was determined using a validated QSAR model for the Mechanism of Action (MechoA) in question (MechoA 1.1, i.e. non-polar narcosis). The QSAR model is based on validated data for a training set of 58 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. - Reference substance (positive control):
- not required
- Key result
- Duration:
- 48 h
- Dose descriptor:
- EC50
- Effect conc.:
- 0.98 mg/L
- Nominal / measured:
- meas. (not specified)
- Conc. based on:
- test mat.
- Basis for effect:
- mobility
- Remarks on result:
- other:
- Remarks:
- 95% CI: 0.83 – 1.2 mg/L
- Details on results:
- Not applicable
- Results with reference substance (positive control):
- Not applicable
- Reported statistics and error estimates:
- 95% confidence interval (α = 0.05): 0.83 - 1.2 mg/L. QSAR statistical parameters are precised in the QMRF, in the attached background material.
- Validity criteria fulfilled:
- yes
- Remarks:
- The substance falls into the applicability domains of the QSAR model.
- Conclusions:
- The 48-h EC50 based on mobility and measured concentrations was determined to be 0.98 mg/L with 95%-Confidence Interval between 0.83 and 1.2 mg/L.
- Executive summary:
A QSAR prediction (KREATiS, 2019) was performed to assess the acute toxicity of the test substance to daphnid. This QSAR 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 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 1.1, i.e. non-polar narcosis). The QSAR model is based on validated data for a training set of 58 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 water solubility value given as the input to the Ecotox module of the iSafeRat® Holistic HA-QSAR falls within the descriptor domain of the model between a log water solubility (in log (mol/L)) of - 4.70 to 0.87.
As discussed in the QMRF for this model withJRC QMRF identifier: Q19-46-51-448, the toxicity of MechoA 1 compounds can be linked thermodynamically to their water solubility values. MechoA 1 is based on the principle of toxicity due to disruption of biological membrane leading to a narcosis effect.
The 48-h EC50 based on mobility and measured concentrations was determined to be 0.98 mg/L with 95%-Confidence interval between 0.83 and 1.2 mg/L.
Referenceopen allclose all
Table 6.1.3/2 : Measured concentrations for Ambramone as % of the nominal values
Nominal values (mg/L) |
Initial medium (%) |
Final medium (%) |
0,19 | 99,2 | 100,7 |
0,34 | 97,1 | 97,8 |
0,60 | 98,3 | 99,7 |
1,10 | 99,4 | 97,8 |
2,00 | 97,1 | 98,2 |
Table 6.1.3/3 : Definitive test - % immobilized daphnids for the controls and the test item treatments
% immobilization after 24h | % immobilization after 48h | |||||||
Rep 1 | Rep 2 | Rep 3 | Rep 4 | Rep 1 | Rep 2 | Rep 3 | Rep 4 | |
water control | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
solvent control | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Ambramone | ||||||||
0.19 mg/L | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
0.34 mg/L | 0 | 0 | 0 | 0 | 0 | 0 | 20 | 20 |
0.60 mg/L | 0 | 0 | 0 | 0 | 20 | 20 | 40 | 40 |
1.10 mg/L | 0 | 0 | 0 | 20 | 60 | 60 | 60 | 40 |
2.00 mg/L | 20 | 20 | 40 | 80 | 100 | 100 | 100 | 100 |
Table 6.1.3/4: Definitive test - detailed calculations of EC50 values for test item
After 24h of testing | after 48h of testing | |
Lowest treatment group | 0.60 mg/L | 0.19 mg/L |
Highest treatment group | 2.00 mg/L | 2.00 mg/L |
Regression slope | 76.4 | 96.2 |
Regression constant | 12.0 | 58.7 |
Coefficient of correlation | r = 0.49 | r = 0.89 |
EC50 (mg/L) | 1.84 | 0.79 |
95% confidence level | 0,70 - 4.82 | 0.42 - 1.47 |
No additional information
Description of key information
iSafeRat® High-Accuracy-Quantitative Structure-Activity Relationship, KREATIS, 2019 :
48h-EC50 = 0.98 mg/L (95% confidence interval: 0.83 – 1.2 mg/L)
Key value for chemical safety assessment
Fresh water invertebrates
Fresh water invertebrates
- Effect concentration:
- 0.98 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, 2012) 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, 2019) 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 1.1, i.e. non-polar narcosis) (Bauer et al., 2018). The QSAR model is based on validated data for a training set of 58 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 0.98 mg/L (95% CI: 0.83 - 1.2 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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