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

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:

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 Daphnia (immobilisation)

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 202 (Daphnia sp. Acute Immobilisation Test)

Principles of method if other than guideline:

The immobility 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) (4). The QSAR model is based on validated data for a training set of 58 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

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):

Daphnia sp.

Details on test organisms:

Results from the following species were used in the regression: Daphnia magna, Daphnia pulex.
No difference in relationship between solubility and ecotoxicity 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

Water media type:

freshwater

Limit test:

no

Total exposure duration:

48 h

Post exposure observation period:

Not applicable

Hardness:

Not applicable

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 dissolved oxygen concentration was more than 60% of the air-saturation value throughout the duration of the test. In exceptional cases where studies with oxygen concentrations lower than 60% were used, all aspects of the study were thoroughly evaluated in order to satisfy the evaluator that the effects found were not due to reduced oxygen concentration (i.e. the study would correctly receive a Klimisch score of 2 under the REACH Regulation (REACH, 2006).

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 or EC50 based on nominal values) were used only when sufficient justification for stability of the test item was determined.
When nominal concentrations from training set data were used, the concentrations of the test substance had been shown to be maintained to within 80% of the nominal concentrations throughout the duration of the study either using analytical verification or by application of a weight of evidence approach that such an assumption was justified. If the deviation from the nominal concentration was >20%, the results were based on the measured concentrations.

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. 202, "Daphnia sp., Acute Immobilisation Test", referenced as Method C.2 of Commission Regulation No. 440/2008.
The immobility 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). The QSAR model is based on validated data for a training set of 58 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.

Reference substance (positive control):

not required

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

19 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other:

Remarks:

95 % CI = 17 - 20 mg/L

Details on results:

Not applicable

Results with reference substance (positive control):

Not applicable

Reported statistics and error estimates:

95% confidence interval (α = 0.05): 17 – 20 mg/L. QSAR statistical parameters are precised in the QMRF, in the attached background material.

No additional information

Validity criteria fulfilled:

yes

Remarks:

The substance falls into the applicability domains of the QSAR model.

Conclusions:

The 48-h EC50 based on mobility and measured concentrations was determined to be 19 mg/L with 95%-Confidence Limit between 17 and 20 mg/L.

Executive summary:

A QSAR prediction was performed to assess the acute toxicity of the test 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 202. 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 immobility 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). The QSAR model is based on validated data for a training set of 58 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 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 - 4.70 to 0.87.

As discussed in the QMRF for this model with JRC QMRF identifier: Q19-46-51-448, the toxicity of MechoA 1 compounds can be linked thermodynamically to their water solubility values. MechoA 1 is based on the principle of toxicity due to disruption of biological membrane leading to a narcosis effect.

The 48-h EC50 based on mobility and measured concentrations was determined to be 19 mg/L with 95%-Confidence Limit between 17 and 20 mg/L.

Description of key information

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

48h-EC50 = 19 mg/L

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

19 mg/L

Additional information

A QSAR prediction was performed to assess the acute toxicity of the test 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 202. 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 immobility 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). The QSAR model is based on validated data for a training set of 58 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 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 - 4.70 to 0.87.

As discussed in the QMRF for this model withJRC QMRF identifier: Q19-46-51-448, the toxicity of MechoA 1 compounds can be linked thermodynamically to their water solubility values. MechoA 1 is based on the principle of toxicity due to disruption of biological membrane leading to a narcosis effect.

The 48-h EC50 based on mobility and measured concentrations was determined to be 19 mg/L with 95%-Confidence Limit between 17 and 20 mg/L.