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Ecotoxicological information

Long-term toxicity to aquatic invertebrates

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Reference
Endpoint:
long-term toxicity to aquatic invertebrates
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
July 01st, 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® High Accuracy QSAR to predict the chronic aquatic toxicity : Long-term toxicity to daphnids

2. MODEL (incl. version number)
iSafeRat® High Accuracy QSAR to predict the chronic aquatic toxicity v1.4.

3. SMILES OR OTHER IDENTIFIERS
CC1(CCCC2(C1CCC3(C2CCO3)C)C)C

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:
OECD Guideline 211 (Daphnia magna Reproduction 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 daphnids as would be expected in a laboratory experiment following OECD Guideline 211 for specific named mechanisms of action. The model provides an in silico prediction for the 21-day EC10 value that can effectively be used in place of an experimental value. The regression based method used to achieve this has been fully validated following the OECD recommendations.
GLP compliance:
no
Specific details on test material used for the study:
-Description: solid, melting point = 80°C (Harlan, 2008)
-Water Solubility: 1.88 mg/L (Harlan, 2009)
-Mechanism of action: MechoA 1.1: non-polar narcosis (Bauer et al., 2018)
Analytical monitoring:
no
Details on sampling:
not applicable
Vehicle:
no
Details on test solutions:
not applicable
Test organisms (species):
Daphnia magna
Details on test organisms:
no information
Test type:
other: QSAR model
Water media type:
freshwater
Limit test:
no
Total exposure duration:
21 d
Remarks on exposure duration:
Results from a test duration of 21 days only were used for Daphnia magna.
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 20 to 23 °C.
pH:
Test results were taken from studies with measured pHs between 6 - 9.
Dissolved oxygen:
The QSAR is based on data from studies performed at acceptable oxygen concentrations.
Salinity:
Not applicable
Conductivity:
no information
Nominal and measured concentrations:
Studies were used only where sufficient evidence was presented to determine that the stubstance was stable under test conditions (i.e. maintened 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 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:
21 d
Dose descriptor:
EC10
Effect conc.:
0.088 mg/L
Nominal / measured:
meas. (not specified)
Conc. based on:
test mat.
Basis for effect:
reproduction
Remarks on result:
other: 95%CI: 0.065 – 0.12 mg/L
Details on results:
The test item falls within the applicability domain of the model and can therefore be considered a reliably prediction for chronic toxicity (21d-EC10) to daphnids. Therefore, this endpoint value can be considered valid for use in risk assessment and classification and labelling.
Results with reference substance (positive control):
not applicable
Reported statistics and error estimates:
95% confidence interval (α = 0.05): 0.065 – 0.12 mg/L.
QSAR statistical parameters are given in the QMRF and the QPRF

Applicability domain analysis:

Descriptor domain

The water solubility value given as the input to the iSafeRat® HA-QSAR for chronic aquatic toxicity (1.88 mg/L, equivalent to subcooled liquid water solubility at 6.61 mg/L or -4.554 in log (mol/L)) falls within the descriptor domain of the model between a log water solubility (in log (mol/L)) of -5.910 to 1.030.

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® HA-QSAR for chronic aquatic toxicity can reliably predict the aquatic toxicity for chemicals with the toxic mechanism of action (MechoA) of non-polar narcosis (MechoA 1.1). The MechoA of molecules is predicted directly from the structure. The test item as an aliphatic ether is expected to exert a MechoA 1.1 and can be taken into account by the model.

Validity criteria fulfilled:
yes
Remarks:
The test item falls within the applicability domain of the model and can therefore be considered a reliably prediction for chronic toxicity (21d-EC10) to daphnids.
Conclusions:
The 21d-EC10 of the test item to daphnids was predicted as 0.088 mg/L.
95% confidence interval (α = 0.05): 0.065 – 0.12 mg/L.
Executive summary:

A QSAR model was used to calculate the chronic toxicity of the test item to daphnid. 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 Guideline for Testing of Chemicals No. 211, "Daphnia magna Reproduction Test" (OECD, 2012). The criterion predicted was the EC10 (10% Effective Concentration), a concentration which is expected to cause an effect of 10% on reproducibility within a period of 21 days.

The chronic toxicity 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 is based on validated data for a training set of 30 chemicals derived from 21-day test on daphnids, for which the concentrations of the test item had been determined by chemical analyses over the test period.

The 21d-EC10 of the test item to daphnids was predicted as 0.088 mg/L with 95% confidence interval (α = 0.05): 0.065 – 0.12 mg/L.

The test item falls within the applicability domain of the model and can therefore be considered a reliably prediction for chronic toxicity (21d-EC10) to daphnids. Therefore, this endpoint value can be considered valid for use in risk assessment and classification and labelling.

Description of key information

QSAR model, iSafeRat® High Accuracy QSAR to predict the chronic aquatic toxicity v1.4, key study, validity 1:

21d-EC10 = 0.088 mg/L (95% CL: 0.065 - 0.12 mg/L).

Key value for chemical safety assessment

EC10, LC10 or NOEC for freshwater invertebrates:
0.088 mg/L

Additional information

To assess the long-term toxicity of the registered substance to aquatic invertebrates, one data point is available.

This value (QSAR-KREATiS, 2019) is assessed as a key datapoint and is a QSAR. This QSAR prediction (iSafeRat® High Accuracy QSAR to predict the chronic aquatic toxicity v1.4) was performed on the registered substance, to assess the chronic toxicity of the 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 211. The criterion predicted was the EC10 (10% Effective Concentration), a concentration which is expected to cause an effect of 10% on reproducibility within a period of 21 days. The chronic toxicity of the daphnids was determined using a validated QSAR for the Mechanism of action (MechoA) in question (MechoA 1.1, i.e. non-polar narcosis). The QSAR is based on validated data for a training set of 30 chemicals derived from 21-day test on daphnids, for which the concentrations of the test item had been determined by chemical analyses over the test period. The 21d-EC10 of the test item to daphnids was predicted as 0.088 mg/L with 95%-Confidence Limit between 0.065 and 0.12 mg/L. The test item falls within the applicability domain of the model and can therefore be considered a reliable prediction for chronic toxicity (21d-EC10) to daphnids.

A testing proposal is included in the dossier to conduct an experimental Daphnia magna reproduction test, according to OECD Guideline 211, on the registered substance. The test on aquatic invertebrates is proposed, since according to the outcome of iSafeRat QSAR model, Daphnia magna is the most sensitive species in chronic exposure. An experimentally- determined EC10 value would allow to conclude appropriately on the environmental classification of the registered substance. After acceptance of the submitted testing proposal for a Daphnia magna reproduction test, by ECHA, and when the new experimental study report is made available, the dossier and the final environmental classification will be updated.