5-hept-6-enyloxolan-2-one

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

09 November 2021

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® – in Silico Algorithms For Environmental Risk And Toxicity

2. MODEL (incl. version number)
iSafeRat® daphEC50 v1.9

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
O=C1CCC(CCCCCC=C)O1

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF

5. APPLICABILITY DOMAIN
See attached Study Report with QPRF in Annex

6. ADEQUACY OF THE RESULT
See attached Study Report with QPRF in Annex

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 2.1, i.e. mono-/poly-esters whose hydrolysis products are narcotics) (Bauer et al., 2018). The purpose of this QSAR model is to accurately predict the acute toxicity to daphnids as would be expected in alaboratory experiment following the OECD Guideline 202 (OECD, 2004) and EC method C.1 (European Commission, 2008). 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.

GLP compliance:

no

Remarks:

QSAR model

Specific details on test material used for the study:

log KOW = 2.66 (Phytosafe, 2005)
Water Solubility: 1.03E+03 mg/L (KREATiS, 2021)
Mechanism of action: MechoA 2.1: mono-/poly-esters whose hydrolysis products are narcotics (Bauer et al., 2018)

Analytical monitoring:

no

Remarks:

QSAR model

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 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 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):

not required

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

47 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): 41 – 54 mg/L.

Details on results:

The test item falls within the applicability domain of the model.

Results with reference substance (positive control):

not applicable

Reported statistics and error estimates:

95% confidence interval (α = 0.05): 41 – 54 mg/L.

Applicability Domain

Descriptor domain
The Subcooled Liquid Water Solubility value (1.03E+03 mg/L or -2.248 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 -0.08 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 ester is expected to exert a MechoA 2.1 and can be taken into account by the model (Bauer et al., 2018).

Validity criteria fulfilled:

yes

Conclusions:

The QSAR model used to achieve the study has been fully validated following the OECD recommendations (OECD, 2004). The test item falls within the applicability domain of the model and was therefore reliably predicted for its 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 ACUTE TOXICITY TO DAPHNIDS (48-HOUR EC50) of the test item was predicted as 47 mg/L. 95% confidence interval (α = 0.05): 41 – 54 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, 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" (OECD, 2004), 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 2.1, i.e. mono-/poly-esters whose hydrolysis products are narcotics) (Bauer et al., 2018). 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 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 TO DAPHNIDS (48-HOUR EC50). Therefore, this endpoint value can be considered valid for use in risk assessment and classification and labelling.

The ACUTE TOXICITY TO DAPHNIDS (48-HOUR EC50) of the test item was predicted as 47 mg/L.
95% confidence interval (α = 0.05): 41 - 54 mg/L

Description of key information

QSAR model, iSafeRat , key study, validity 1:

48h-EC50 = 47 mg/L (95% CL: 41- 54 mg/L).

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Dose descriptor:

EC50

Effect concentration:

47 mg/L

Additional information

To assess the short-term toxicity of the registered substance to aquatic invertebrates, one key study QSAR is available.

 

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, 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" (OECD, 2004), 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 2.1, i.e. mono-/poly-esters whose hydrolysis products are narcotics) (Bauer et al., 2018). 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 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 TO DAPHNIDS (48-HOUR EC50). Therefore, this endpoint value can be considered valid for use in risk assessment and classification and labelling.

The ACUTE TOXICITY TO DAPHNIDS (48-HOUR EC50) of the test item was predicted as 47 mg/L.
95% confidence interval (α = 0.05): 41 - 54 mg/L