5-hept-6-enyloxolan-2-one

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Endpoint:

toxicity to aquatic algae and cyanobacteria

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® algErC50 v1.9
iSafeRat® algNOEC v1.1

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 and QPRF in Annex

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 201 (Freshwater Alga and Cyanobacteria, Growth Inhibition Test)

Deviations:

not applicable

Remarks:

QSAR model

Principles of method if other than guideline:

The TOXICITY TO ALGAE (72-HOUR ErC50 and NOECr) was determined using iSafeRat® algEC50 and iSafeRat® algNOEC, two validated QSAR models 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 QSAR model is based on validated data for a training set of 44 chemicals derived from 72-hour ErC50 test on algae, for which the concentrations of the test item had been determined by chemical analyses over the test period. The 72-hour NOEC was not determined because the QSAR model iSafeRat® algNOEC is only applicable for chemicals with the mechanism of action of non-polar narcosis (MechoA 1.1).

GLP compliance:

no

Remarks:

QSAR model

Specific details on test material used for the study:

log KOW = 2.66 (Phytosafe, 2005)
Water Solubility: 1.030E+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

Remarks:

QSAR model

Details on test solutions:

not applicable

Test organisms (species):

other: Pseudokirchneriella subcapitata, Desmodesmus subspicatus, Scenedesmus quadricauda

Details on test organisms:

No difference in terms of toxic mechanism of action between algae (or indeed other) aquatic species is expected. Any observed differences may be attributed to lifestyle related parameters and relative duration of study versus cell size 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:

72 h

Remarks on exposure duration:

Results from a test duration of 72 hours only were used for this algorithm.

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 25 °C depending on the species used to construct the models. This small difference is not expected to significantly contribute to the variability of the values found in experimental data.

pH:

Test results were preferably taken from studies with measured pHs between 6 - 9. However it is recognized that in some cases (due to high luminosity) the pH may increase in the control and lower concentrations (which do not cause significant
effect over the study period). This pH increase did not generally disqualify the study from being used in the test and validation set for non-polar chemicals.

Dissolved oxygen:

The temperatures varied from approximately 20 to 25 °C depending on the species used to construct the algorithm. This small difference is not expected to contribute to the variability of the ErC50 values found in experimental data.

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 measured initial concentration throughout the test) or, if not, the result
was based on measured concentrations as geometric mean.

Details on test conditions:

Following the guideline OECD 201, all studies were from a static test design. 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:

72 h

Dose descriptor:

EC50

Effect conc.:

46 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

growth rate

Remarks on result:

other: 95CI: [40 ; 54] mg/L

Details on results:

The test item falls only within the applicability domain of the model iSafeRat® algEC50 but it does not fall within the model iSafeRat® algNOEC. Therefore, only the 72-HOUR ErC50 was reliably predicted.

Results with reference substance (positive control):

not applicable

Reported statistics and error estimates:

95% confidence interval (α = 0.05) for 72h-ErC50: 40 – 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® algErC50 model falls within the descriptor domain of the model between a Subcooled Liquid Water Solubility of -5.57 to 0.93 in log10 (mol/L).

Structural fragment domain
All chemical groups within the molecular structure are taken into account by the models.

Mechanistic domain
Currently, the iSafeRat® algErC50 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 iSafeRat® algNOECr model can only reliably predict the aquatic toxicity for chemicals with the mechanism of action of non-polar narcosis (MechoA 1.1).

 

The MechoA of molecules is predicted directly from the structure. The test item as an aster is expected to exert a MechoA 2.1 and can only be taken into account by the QSAR model iSafeRat® algErC50 (Bauer et al., 2018). The 72-hour NOEC is not determined because the QSAR model iSafeRat® algNOEC is only applicable for chemicals with the mechanism of action of non-polar narcosis (MechoA 1.1).

Validity criteria fulfilled:

yes

Conclusions:

The QSAR model used to achieve the study has been fully validated following the OECD recommandations (OECD, 2004). The test item falls within the applicability domain of the model and was therefore reliably predicted for its TOXICITY TO ALGAE (72-HOUR ErC50). However, the 72-hour NOEC was not determined because the QSAR model iSafeRat® algNOEC is only applicable for chemicals with the mechanism of action of non-polar narcosis (MechoA 1.1). Nevertheless, this endpoint value can be considered valid for use in risk assessment and classification and labelling.
The TOXICITY TO ALGAE (72-HOUR ErC50) of the test item was predicted as 46 mg/L.
95% confidence interval (α = 0.05) for 72h-ErC50: 40 – 54 mg/L.
95% confidence interval (α = 0.05) for 72h-NOECr: not determined

Executive summary:

Two Quantitative Structure-Activity Relationship (QSAR) models were used to calculate the TOXICITY TO ALGAE (72-HOUR ErC50 and NOECr) of the test item. These QSAR models have been validated to be compliant with the OECD  recommendations for QSAR modeling (OECD, 2004) and predict the endpoint values which would be expected when testing the substance under experimental conditions in a laboratory following the Guideline for Testing of Chemicals No. 201, "Freshwater Alga and Cyanobacteria, Growth Inhibition Test" (OECD, 2006), referenced as Method C.3 of Commission Regulation No. 440/2008 (European Commission, 2008). The criterions predicted were the Median Effective Concentration (ErC50), a statistically derived concentration which is expected to cause 50% inhibition of intrinsic rate of growth of the test system and the No Observed Effect Concentration (NOECr), a tested concentration which is expected to cause no effect on intrinsic rate of growth of the test system. Both criterions were determined for a period exposure of 72 hours.

 

The TOXICITY TO ALGAE (72-HOUR ErC50 and NOECr) was determined using iSafeRat® algEC50, 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 QSAR model is based on validated data for a training set of 44 chemicals derived from 72-hour ErC₅₀ test on algae, for which the concentrations of the test item had been determined by chemical analyses over the test period. The 72-hour NOEC was not determined because the QSAR model iSafeRat® algNOEC is only applicable for chemicals with the mechanism of action of non-polar narcosis (MechoA 1.1).

 

The QSAR model used to achieve the study has been fully validated following the OECD recommandations (OECD, 2004). The test item falls within the applicability domain of the model and was therefore reliably predicted for its TOXICITY TO ALGAE (72-HOUR ErC50). However, the 72-hour NOEC was not determined because the QSAR model iSafeRat® algNOEC is only applicable for chemicals with the mechanism of action of non-polar narcosis (MechoA 1.1). Nevertheless, this endpoint value can be considered valid for use in risk assessment and classification and labelling.

 

The TOXICITY TO ALGAE (72-HOUR ErC50) of the test item was predicted as 46 mg/L.
95% confidence interval (α = 0.05) for 72h-ErC50: 40 – 54 mg/L.
95% confidence interval (α = 0.05) for 72h-NOECr: not determined

Description of key information

QSAR models, iSafeRat QSAR, key studies:

72h-ErC50 = 46 mg/L (95% CL: 40 - 54 mg/L)

72h-NOECr =not determinated

Key value for chemical safety assessment

EC50 for freshwater algae:

46 mg/L

Additional information

To assess the toxicity of the registered substance to aquatic algae,one key study QSAR is available

Two Quantitative Structure-Activity Relationship (QSAR) models were used to calculate the TOXICITY TO ALGAE (72-HOUR ErC50 and NOECr) of the test item. These QSAR models have been validated to be compliant with the OECD  recommendations for QSAR modeling (OECD, 2004) and predict the endpoint values which would be expected when testing the substance under experimental conditions in a laboratory following the Guideline for Testing of Chemicals No. 201, "Freshwater Alga and Cyanobacteria, Growth Inhibition Test" (OECD, 2006), referenced as Method C.3 of Commission Regulation No. 440/2008 (European Commission, 2008). The criterions predicted were the Median Effective Concentration (ErC50), a statistically derived concentration which is expected to cause 50% inhibition of intrinsic rate of growth of the test system and the No Observed Effect Concentration (NOECr), a tested concentration which is expected to cause no effect on intrinsic rate of growth of the test system. Both criterions were determined for a period exposure of 72 hours.

 

The TOXICITY TO ALGAE (72-HOUR ErC50 and NOECr) was determined using iSafeRat® algEC50, 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 QSAR model is based on validated data for a training set of 44 chemicals derived from 72-hour ErC₅₀ test on algae, for which the concentrations of the test item had been determined by chemical analyses over the test period. The 72-hour NOEC was not determined because the QSAR model iSafeRat® algNOEC is only applicable for chemicals with the mechanism of action of non-polar narcosis (MechoA 1.1).

 

The QSAR model used to achieve the study has been fully validated following the OECD recommandations (OECD, 2004). The test item falls within the applicability domain of the model and was therefore reliably predicted for its TOXICITY TO ALGAE (72-HOUR ErC50). However, the 72-hour NOEC was not determined because the QSAR model iSafeRat® algNOEC is only applicable for chemicals with the mechanism of action of non-polar narcosis (MechoA 1.1). Nevertheless, this endpoint value can be considered valid for use in risk assessment and classification and labelling.

 

The TOXICITY TO ALGAE (72-HOUR ErC50) of the test item was predicted as 46 mg/L.
95% confidence interval (α = 0.05) for 72h-ErC50: 40 – 54 mg/L.
95% confidence interval (α = 0.05) for 72h-NOECr: not determined