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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Ecotoxicological information

Long-term toxicity to fish

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Administrative data

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Endpoint:
fish early-life stage toxicity
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
In accordance with column 2 of REACH annex IX, further testing on the long-term effects on aquatic organisms does not need to be conducted as the chemical safety assessment does not indicate a need for further investigation.
Endpoint:
fish early-life stage toxicity
Type of information:
(Q)SAR
Remarks:
QSAR result on the C6 isomers of the transformation product of the registered substance
Adequacy of study:
supporting study
Study period:
Run on 2016-01
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
Remarks:
(Q)SAR method with established scientific validity. The substance, C6 isomers of the transformation product of the registered substance, falls within the applicability domain of the model.
Justification for type of information:
1. SOFTWARE
EPISUITE v4.1

2. MODEL (incl. version number)
ECOSAR v1.11

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
C6 isomers of the transformation product of the registered substance: C1C(C)(C)CCCC1C(C)OC(C)(C)COH
log Pow: 4.33 (experimental result)

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Neutral Organics SAR document in "Attached background material".

5. APPLICABILITY DOMAIN
See attached QPRF

6. ADEQUACY OF THE RESULT
See attached QPRF
Qualifier:
according to guideline
Guideline:
other: REACH guidance on QSARs R.6, May 2008
Deviations:
no
Principles of method if other than guideline:
See attached QPRF
GLP compliance:
no
Remarks:
(not relevant)
Specific details on test material used for the study:
- log Pow: 4.33 (experimental result)
Details on sampling:
Not applicable
Details on test solutions:
Not applicable
Test organisms (species):
no data
Details on test organisms:
Not applicable
Test type:
not specified
Water media type:
not specified
Post exposure observation period:
Not applicable
Hardness:
Not applicable
Test temperature:
Not applicable
pH:
Not applicable
Dissolved oxygen:
Not applicable
Salinity:
Not applicable
Nominal and measured concentrations:
Not applicable
Details on test conditions:
Not applicable
Key result
Dose descriptor:
other: ChV
Effect conc.:
0.19 mg/L
Remarks on result:
other: ECOSAR Class: Neutral Organics
Details on results:
Validity of model:
1. Defined Endpoint: Long term toxicity to fish (chronic value).
2. Unambigous algorithm: Linear regression QSAR; Log ChV (mmol/L) = -0.8508*log Kow + 0.6063.
To convert the ChV from mmol/L to mg/L, multiply by the molecular weight.
3. Applicability domain: applicable to chemicals with log Kow less than 8.0 and molecular weight less than 1000 g/mol. The model can be suitable for chemicals class of neutral organic.
4. Statistical characteristics: N = 46+7 and the coefficient of determination R² = 0.7393.
5. Mechanistic interpretation: related to the partitioning of the substance from water into the organisms lipid phase.

Adequacy of prediction: the substance falls within the applicability domain described above and therefore the predicted value can be considered reliable. For more information, see Neutral Organics SAR document in "Attached background material".
Results with reference substance (positive control):
Not applicable
Reported statistics and error estimates:
N = 46+7 and the coefficient of determination R² = 0.7393.

No additional information

Validity criteria fulfilled:
yes
Conclusions:
The C6 isomers of the transformation product of the registered substance was predicted to have a chronic value ChV of 0.19 mg/L to fish. The substance falls within the applicability domain and therefore the predicted value can be considered reliable.
Executive summary:

The long term toxicity to fish of the C6 isomers of the transformation product of the registered substance was estimated using the ECOSAR v1.11 QSAR model available from the U.S. EPA.

The estimation chronic value ChV was 0.19 mg/L (neutral organics class), calculated from a measured log Kow value (4.33) and a linear regression:

Log ChV (mmol/L) = -0.8508*log Kow + 0.6063

The substance falls within the applicability domain and therefore the predicted value can be considered reliable.

Endpoint:
fish early-life stage toxicity
Type of information:
(Q)SAR
Remarks:
QSAR result on the C6 isomers of the transformation product of the registered substance
Adequacy of study:
supporting study
Study period:
From 2016-01-05 to 2016-01-06
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
Remarks:
QSAR value. The substance, C6 isomers of the transformation product of the registered substance, falls into the applicability domain of the model QSAR
Justification for type of information:
1. SOFTWARE
iSafeRat® High Accuracy QSAR to predict the chronic aquatic toxicity : Long-term toxicity to fish

2. MODEL (incl. version number)
iSafeRat® High Accuracy QSAR to predict the chronic aquatic toxicity v1.1.

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
C6 isomers of the transformation product of the registered substance: C1C(C)(C)CCCC1C(C)OC(C)(C)COH
Water solubility = 35.0 mg/L (KREATIS internal study, 2015), derived using the log Kow experimental value at 4.33

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 210 (Fish, Early-Life Stage Toxicity 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 chronic toxicity to fish as would be expected in a laboratory experiment following OECD Guideline 210 for specific, named modes of action, to provide a value that can effectively replace a 28-day NOEC value from an experimental study. The regression based method used to achieve this has been fully validated following the OECD (2004) recommendations (refer to the QMRF with KREATiS QMRF identifier: KTS/QMRF/CHR/01 for further details).
GLP compliance:
no
Specific details on test material used for the study:
- Mode of action: non-polar narcotic (MOA 1 or MechoA 1.1)
- Log Kow = 4.33 (from experimental study)
- Water solubility = 35.0 mg/L (KREATIS internal study, 2015)
Analytical monitoring:
no
Details on sampling:
Not applicable
Vehicle:
no
Details on test solutions:
Not applicable
Test organisms (species):
other: Danio rerio, Pimephales promelas, Oryzias latipes, Leuciscus idus, Jordanella floridae, Cyprinus carpio
Details on test organisms:
Results from the following species were used in the regression:
Danio rerio, Pimephales promelas, Oryzias latipes, Leuciscus idus, Jordanella floridae, Cyprinus carpio

Following the principles of Phase Equilibrium Thermodynamics, for narcotic substances, no difference in relationship between solubility and ecotoxicity between fish freshwater species is expected. Any observed differences may be attributed to lifestyle related parameters (e.g. relative differences in storage lipid content between species) and relative duration of study versus bodysize rather than to a specific toxic mechanism causing species differences. In this case, for MOA 1 or MechoA 1.1, no differences were observed in activity based toxicity for the species used.
Test type:
other: QSAR
Water media type:
freshwater
Limit test:
no
Total exposure duration:
28 d
Remarks on exposure duration:
Only results from a test duration of 14* to 32 days were included. The median study duration was 28 days. *These results were from short term embryo studies where the log KOW of the substance was <4 and equilibrium was considered to be reached.
Post exposure observation period:
None
Hardness:
The QSAR is based on data from studies performed at acceptable hardness to ensure control survival.
Test temperature:
The temperatures varied from approximately 21 to 27 °C depending on the fish species used to construct the algorithm.
pH:
Test results were taken from studies with measured pHs between 6.0 - 8.5.
Dissolved oxygen:
The QSAR is based on data from studies performed at acceptable oxygen concentrations (generally >60%).
Salinity:
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 NOEC based on nominal values) were used only when sufficient justification for stability of the test was determined.
Details on test conditions:
Preferentially results from a flow-through test were used. However semi-static with daily renewal of test solutions and the control was 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:
28 d
Dose descriptor:
NOEC
Effect conc.:
0.39 mg/L
Nominal / measured:
meas. (not specified)
Conc. based on:
test mat.
Basis for effect:
other: growth or reproduction
Remarks on result:
other: 95% CL: 0.30-0.53 mg/L
Details on results:
The predicted value is reliable since the test substance falls within the applicability domain of the model. The value of water solubility value of the test substance is within descriptor domain of the model between log water solubility (in log (mol/L)) of -5.56 to -0.32. Moreover the test substance is attributed to the class of non-polar narcotic compounds.
Results with reference substance (positive control):
Not applicable
Reported statistics and error estimates:
95% CL: 0.30-0.53 mg/L
QSAR statistical parameters are given in the QMRF and the QPRF

No additional information

Validity criteria fulfilled:
yes
Remarks:
The substance falls into the applicability domain of the QSAR model.
Conclusions:
The 28d-NOEC of the C6 isomers of the transformation product of the registered substance was determined to be 0.39 mg/L with 95%-Confidence Limit between 0.30 and 0.53 mg/L.
Executive summary:

A QSAR model model was used to calculate the chronic toxicity of the C6 isomers of the transformation product of the registered substance to fish. 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 OECD Guideline 210. The criterion predicted was the NOEC (No Observed Effect Concentration), a tested concentration which is observed to cause no effect on growth or survival within a period of 28 days.

The chronic toxicity to fish was determined using a validated QSAR for the Mode of Action in question (MOA 1 or MechoA 1.1, non-polar narcosis). The QSAR is based on validated data for a training set of 26 chemicals derived from 14 to 32-day test on fish, for which the concentrations of the test item had been determined by chemical analyses over the test period. The water solubility of the substance given as input was predicted by the iSafeRat® solubility module using the experimental log Kow value of the substance, measured at 4.33. The substance falls within the applicability domain of the model as demonstrated in the QPRF.

The 28d-NOEC of the test item was determined to be 0.39 mg/L with 95%-Confidence Limit between 0.30 and 0.53 mg/L.

Endpoint:
fish early-life stage toxicity
Type of information:
(Q)SAR
Remarks:
QSAR result on the C7 isomer of the transformation product of the registered substance
Adequacy of study:
supporting study
Study period:
Run on 2016-01
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
Remarks:
(Q)SAR method with established scientific validity. The substance, C7 isomer of the transformation product of the registered substance, falls within the applicability domain of the model.
Justification for type of information:
1. SOFTWARE
EPISUITE v4.1

2. MODEL (incl. version number)
ECOSAR v1.11

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
C7 isomer of the transformation product of the registered substance: OCC(C)(C)OC1CC(C)(C)CCCC1C
log Pow: 4.40 (KREATIS QSAR - iSafeRat v1.5, 2016)

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Neutral Organics SAR document in "Attached background material".

5. APPLICABILITY DOMAIN
See attached QPRF

6. ADEQUACY OF THE RESULT
See attached QPRF
Qualifier:
according to guideline
Guideline:
other: REACH guidance on QSARs R.6, May 2008
Deviations:
no
Principles of method if other than guideline:
See attached QPRF
GLP compliance:
no
Remarks:
(not relevant)
Specific details on test material used for the study:
- log Pow: 4.40 (KREATIS QSAR - iSafeRat v1.5, 2016)
Details on sampling:
Not applicable
Details on test solutions:
Not applicable
Test organisms (species):
no data
Details on test organisms:
Not applicable
Test type:
not specified
Water media type:
not specified
Post exposure observation period:
Not applicable
Hardness:
Not applicable
Test temperature:
Not applicable
pH:
Not applicable
Dissolved oxygen:
Not applicable
Salinity:
Not applicable
Nominal and measured concentrations:
Not applicable
Details on test conditions:
Not applicable
Key result
Dose descriptor:
other: ChV
Effect conc.:
0.17 mg/L
Remarks on result:
other: ECOSAR Class: Neutral Organics
Details on results:
Validity of model:
1. Defined Endpoint: Long term toxicity to fish (chronic value).
2. Unambigous algorithm: Linear regression QSAR; Log ChV (mmol/L) = -0.8508*log Kow + 0.6063.
To convert the ChV from mmol/L to mg/L, multiply by the molecular weight.
3. Applicability domain: applicable to chemicals with log Kow less than 8.0 and molecular weight less than 1000 g/mol. The model can be suitable for chemicals class of neutral organic.
4. Statistical characteristics: N = 46+7 and the coefficient of determination R² = 0.7393.
5. Mechanistic interpretation: related to the partitioning of the substance from water into the organisms lipid phase.

Adequacy of prediction: the substance falls within the applicability domain described above and therefore the predicted value can be considered reliable. For more information, see Neutral Organics SAR document in "Attached background material".
Results with reference substance (positive control):
Not applicable
Reported statistics and error estimates:
N = 46+7 and the coefficient of determination R² = 0.7393.

No additional information

Validity criteria fulfilled:
yes
Conclusions:
The C7 isomer of the transformation product of the registered substance was predicted to have a chronic value ChV of 0.17 mg/L to fish. The substance falls within the applicability domain and therefore the predicted value can be considered reliable.
Executive summary:

The long term toxicity to fish of the C7 isomer of the transformation product of the registered substance was estimated using the ECOSAR v1.11 QSAR model available from the U.S. EPA.

The estimation chronic value ChV was 0.17 mg/L (neutral organics class), calculated from an estimated log Kow value (4.40) and a linear regression:

Log ChV (mmol/L) = -0.8508*log Kow + 0.6063

The substance falls within the applicability domain and therefore the predicted value can be considered reliable.

Endpoint:
fish early-life stage toxicity
Type of information:
(Q)SAR
Remarks:
QSAR result on the C7 isomer of the transformation product of the registered substance
Adequacy of study:
supporting study
Study period:
From 2016-03-14 to 2016-03-16
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
Remarks:
QSAR value. The substance, C7 isomer of the transformation product of the registered substance, falls into the applicability domain of the model QSAR
Justification for type of information:
1. SOFTWARE
iSafeRat® High Accuracy QSAR to predict the chronic aquatic toxicity : Long-term toxicity to fish

2. MODEL (incl. version number)
iSafeRat® High Accuracy QSAR to predict the chronic aquatic toxicity v1.1.

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
C7 isomer of the transformation product of the registered substance: OCC(C)(C)OC1CC(C)(C)CCCC1C
Water solubility = 29.1 mg/L (KREATiS – Internal Study (2016))

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 210 (Fish, Early-Life Stage Toxicity 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 chronic toxicity to fish as would be expected in a laboratory experiment following OECD Guideline 210 for specific, named modes of action, to provide a value that can effectively replace a 28-day NOEC value from an experimental study. The regression based method used to achieve this has been fully validated following the OECD (2004) recommendations (refer to the QMRF with KREATiS QMRF identifier: KTS/QMRF/CHR/01 for further details).
GLP compliance:
no
Specific details on test material used for the study:
- Mode of action: non-polar narcotic (MOA 1 or MechoA 1.1)
- log Kow : 4.40 (KREATIS, 2016)
- Water solubility = 29.1 mg/L (KREATIS internal study, 2016)
Analytical monitoring:
no
Details on sampling:
Not applicable
Vehicle:
no
Details on test solutions:
Not applicable
Test organisms (species):
other: Danio rerio, Pimephales promelas, Oryzias latipes, Leuciscus idus, Jordanella floridae, Cyprinus carpio
Details on test organisms:
Results from the following species were used in the regression:
Danio rerio, Pimephales promelas, Oryzias latipes, Leuciscus idus, Jordanella floridae, Cyprinus carpio

Following the principles of Phase Equilibrium Thermodynamics, for narcotic substances, no difference in relationship between solubility and ecotoxicity between fish freshwater species is expected. Any observed differences may be attributed to lifestyle related parameters (e.g. relative differences in storage lipid content between species) and relative duration of study versus bodysize rather than to a specific toxic mechanism causing species differences. In this case, for MOA 1 or MechoA 1.1, no differences were observed in activity based toxicity for the species used.
Test type:
other: QSAR
Water media type:
freshwater
Limit test:
no
Total exposure duration:
28 d
Remarks on exposure duration:
Only results from a test duration of 14* to 32 days were included. The median study duration was 28 days. *These results were from short term embryo studies where the log KOW of the substance was <4 and equilibrium was considered to be reached.
Post exposure observation period:
None
Hardness:
The QSAR is based on data from studies performed at acceptable hardness to ensure control survival.
Test temperature:
The temperatures varied from approximately 21 to 27 °C depending on the fish species used to construct the algorithm.
pH:
Test results were taken from studies with measured pHs between 6.0 - 8.5.
Dissolved oxygen:
The QSAR is based on data from studies performed at acceptable oxygen concentrations (generally >60%).
Salinity:
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 NOEC based on nominal values) were used only when sufficient justification for stability of the test was determined.
Details on test conditions:
Preferentially results from a flow-through test were used. However semi-static with daily renewal of test solutions and the control was 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:
28 d
Dose descriptor:
NOEC
Effect conc.:
0.34 mg/L
Nominal / measured:
meas. (not specified)
Conc. based on:
test mat.
Basis for effect:
other: growth or reproduction
Remarks on result:
other: 95% CL: 0.25-0.46 mg/L
Details on results:
The predicated value is reliable since the test substance falls within the applicability domain of the model. The value of water solubility value of the test substance is within descriptor domain of the model between log water solubility (in log (mol/L)) of -5.56 to -0.32. Moreover the test substance is attributed to the class of non-polar narcotic compounds.
Results with reference substance (positive control):
Not applicable
Reported statistics and error estimates:
95% CL: 0.25-0.46 mg/L
QSAR statistical parameters are given in the QMRF and the QPRF

No additional information

Validity criteria fulfilled:
yes
Remarks:
The substance falls into the applicability domain of the QSAR model.
Conclusions:
The 28d-NOEC of the C7 isomer of the transformation product of the registered substance to fish was determined to be 0.34 mg/L with 95%-Confidence Limit between 0.25 and 0.46 mg/L.
Executive summary:

A QSAR model model was used to calculate the chronic toxicity of the C7 isomer of the transformation product of the registered substance to fish. 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 OECD Guideline 210. The criterion predicted was the NOEC (No Observed Effect Concentration), a tested concentration which is observed to cause no effect on growth or survival within a period of 28 days.

The chronic toxicity to fish was determined using a validated QSAR for the Mode of Action in question (MOA 1 or MechoA 1.1, non-polar narcosis). The QSAR is based on validated data for a training set of 26 chemicals derived from 14 to 32-day test on fish, for which the concentrations of the test item had been determined by chemical analyses over the test period. The water solubility of the substance given as input was predicted by the iSafeRat® solubility module. The substance falls within the applicability domain of the model as demonstrated in the QPRF.

The 28d-NOEC of the test item to fish was determined to be 0.34 mg/L with 95%-Confidence Limit between 0.25 and 0.46 mg/L.

Description of key information

In accordance with column 2 of REACH annex IX, further testing on the long-term effects on aquatic organisms does not need to be conducted for the registered substance as the chemical safety assessment does not indicate a need for further investigation. Therefore, a long-term toxicity study on the registered substance to fish is not needed.

Key value for chemical safety assessment

Additional information

In accordance with column 2 of REACH annex IX, further testing on the long-term effects on aquatic organisms does not need to be conducted for the registered substance as the chemical safety assessment does not indicate a need for further investigation. Therefore, a long-term toxicity study on the registered substance to fish is not needed.

In addition, the chronic toxicity of the transformation product (C6 and C7 isomers) of the registered substance, to fish was estimated using two QSAR models. The two QSAR models were ECOSAR v1.11 and iSafeRat High Accuracy QSAR v1.1. Both QSAR results were considered reliable as the substances, C6 and C7 isomers of the transformation product of the registered substance, fall within the applicability domain of the models. The estimated chronic values for C6 isomers were 0.19 mg/L (ChV) and 0.39 mg/L (28d-NOEC), using ECOSAR v1.11 and iSafeRat High Accuracy QSAR v1.1, respectively. The estimated chronic values for C7 isomer were 0.17 mg/L (ChV) and 0.34 mg/L (28d-NOEC), using ECOSAR v1.11 and iSafeRat High Accuracy QSAR v1.1, respectively. The worst case endpoint value, estimated at 0.17 mg/L for the C7 isomer, is chosen as key data for the long-term toxicity of the transformation product of the registered substance to fish.

These data demonstrate that the transformation product of the registered substance is not Toxic (T) in the context of PBT assessment.