2H-Pyran, tetrahydro-3-(phenylmethyl)-

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:

December 13th, 2018

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 algae (inhibition of the exponential growth rate)

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
c1ccccc1CC2COCCC2

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 201 (Alga, Growth Inhibition Test)

Deviations:

not applicable

Remarks:

(QSAR model)

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method C.3 (Algal Inhibition 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 toxicity to algae as would be expected in a laboratory experiment following the OECD Guideline 201 and EC method C.3 for specific, named modes of action to provide a value that can effectively replace a 72-hour ErC50 value from an experimental study. The regression is method used to achieve this has been fully validated following the OECD (2004) recommendations (refer to the QMRF with JRC/KREATiS QMRF identifier: Q19-46-51-448 for further details).

GLP compliance:

no

Specific details on test material used for the study:

- Mechanism of action : MechoA 1.1, non-polar narcosis
- Water solubility : 490 mg/L

Analytical monitoring:

not required

Remarks:

QSAR

Details on sampling:

Not applicable

Vehicle:

no

Details on test solutions:

Not applicable

Test organisms (species):

other: Pseudokirchneriella subcapitata, Desmodesmus subspicatus, Scenedesmus quadricauda

Details on test organisms:

Results from the following species were used in the regression: Pseudokirchneriella subcapitata, Desmodesmus subspicatus, Scenedesmus quadricauda.
No difference in relationship between solubility and ecotoxicity 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 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:

72 h

Remarks on exposure duration:

None

Post exposure observation period:

Not applicable

Hardness:

Not applicable

Test temperature:

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.

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:

Not specified

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 ErC50 based on nominal values) were used only when sufficient justification for stability of the test item was determined.

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. 201, "Freshwater Alga and Cyanobacteria, Growth Inhibition Test", referenced as Method C.3 of Commission Regulation No. 440/2008. The criterion predicted was the ErC50 (Median Effective Concentration for specific growth rate), a statistically derived concentration which is expected to cause 50% inhibition of intrinsic rate of growth of the test system within a period of 72 hours.

Reference substance (positive control):

no

Remarks:

QSAR model

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

18 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

growth rate

Remarks on result:

other: 95% CL: 16 - 20 mg/L

Details on results:

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 - 4.38 to 0.49.
The test substance is attributed to the class of non-polar narcotic compounds (MechoA 1.1).

Results with reference substance (positive control):

Not applicable

Reported statistics and error estimates:

95% CL: 16 - 20 mg/L.
QSAR statistical parameters are given in the QMRF and the QPRF, see the attached background material.

No additional information

Validity criteria fulfilled:

yes

Remarks:

The substance falls into applicability domain of the QSAR model.

Conclusions:

The 72-h ErC50 based on measured concentrations was determined to be 18 mg/L with 95%-Confidence Limit between 16 and 20 mg/L.

Executive summary:

A QSAR prediction (KREATiS, 2018) was performed to assess the inhibition of growth to algae of the test substance. 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 201. The criterion predicted was the ErC50 (Median Effective Concentration for specific growth rate), a statistically derived concentration which is expected to cause 50% inhibition of intrinsic rate of growth of the test system within a period of 72 hours.

 

The growth inhibition of algae was determined using a validated QSAR for the Mechanism of Action (MechoA) 1.1, non-polar narcosis. This QSAR is based on validated data for a training set of 40 chemicals derived from 72 -hour ErC50 test on algae, for which the concentrations of the test substance 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 - 4.38 to 0.49. The substance falls within the applicability domain of the model as demonstrated in the QPRF.

The 72-h ErC50 based on measured concentrations was determined to be 18 mg/L with 95%-Confidence Limit between 16 and 20 mg/L.

Description of key information

iSafeRat® High-Accuracy-Quantitative Structure-Activity Relationship, KREATIS, 2018 :

72h-EC50 = 18 mg/L

Key value for chemical safety assessment

EC50 for freshwater algae:

18 mg/L

Additional information

A QSAR prediction (KREATiS, 2018) was performed to assess the inhibition of growth to algae of the test substance. 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 201. The criterion predicted was the ErC50 (Median Effective Concentration for specific growth rate), a statistically derived concentration which is expected to cause 50% inhibition of intrinsic rate of growth of the test system within a period of 72 hours.

 

The growth inhibition of algae was determined using a validated QSAR for the Mechanism of Action (MechoA) 1.1, non-polar narcosis. This QSAR is based on validated data for a training set of 40 chemicals derived from 72 -hour ErC50 test on algae, for which the concentrations of the test substance 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 - 4.38 to 0.49. The substance falls within the applicability domain of the model as demonstrated in the QPRF.

The 72-h ErC50 based on measured concentrations was determined to be 18 mg/L with 95%-Confidence Limits between 16 and 20 mg/L.