4-allyl-2-methoxyphenyl acetate

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

2017

Reliability:

2 (reliable with restrictions)

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® HA-QSAR toolbox v2.1

2. MODEL (incl. version number)
iSafeRat® holistic HA-QSAR v1.7

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
O=C(Oc(c(OC)cc(c1)CC=C)c1)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

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Deviations:

not applicable

Remarks:

(QSAR model)

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method C.2 (Acute Toxicity for Daphnia)

Deviations:

not applicable

Remarks:

(QSAR model)

Principles of method if other than guideline:

The purpose of this QSAR model is to accurately predict the acute toxicity to daphnid as would be expected in a laboratory experiment following OECD Guideline 202 (1) and EC method C.2 (2) for specific, named modes of action to provide a value that can effectively replace a 48-hour EC50 value from an experimental study. The regression based method used to achieve this has been fully validated following the OECD (2004) (3) recommendations (refer to the QMRF report with JRC/KREATiS QMRF identifier: Q19-46-51-448 for further details).

GLP compliance:

no

Specific details on test material used for the study:

- Mode of action: monoester MOA
- Water solubility: 410 mg/L (from experimental study)

Analytical monitoring:

no

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:

Results from the following species were used in the regression: Daphnia magna, Daphnia pulex.
Following the principles of Phase Equilibrium Thermodynamics, for narcotic substances, 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. In this case, for ester compounds, no differences were observed in activity based toxicity for the 2 species used.

Test type:

other: QSAR

Water media type:

freshwater

Limit test:

no

Total exposure duration:

48 h

Remarks on exposure duration:

none

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:

The QSAR is based on data from studies performed at acceptable pH between 6.0 - 9.0.

Dissolved oxygen:

The QSAR is based on data from studies performed at acceptable oxygen concentrations (generally >60%).

Salinity:

Not applicable.

Nominal and measured concentrations:

The QSAR is based on data from studies performed using measured concentrations or with acceptable stability.

Details on test conditions:

Not applicable

Reference substance (positive control):

no

Remarks:

QSAR model

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

33 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: 95% CL: 28 - 39 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 regression domain of the model between a log water solubility (in log (mol/L)) of - 4.79 to 0.93 where baseline toxicity can be accurately experimentally measured and predicted.

Results with reference substance (positive control):

Not applicable

Reported statistics and error estimates:

95% CL: 28 - 39 mg/L
QSAR statistical parameters are given in the QMRF and the QPRF.

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 33 mg/L with 95%-Confidence Limit between 28 and 39 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 for the Mode of Action in question (mono and poly-esters MOA). The QSAR model is based on validated data for a training set of 41 mono-esters compounds derived from 48-hour tests on daphnids, for which the concentrations of the test substance had been determined by chemical analyses over the test period. The water solubility of the substance given as input was experimentally measured at 410 mg/L. The substance falls within the applicability domain of the model as demonstrated in the QPRF.

The 48-h EC50 based on mobility and measured concentrations was determined to be 33 mg/L with 95%-Confidence Limit between 28 and 39 mg/L.

Reference 2

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

Run on 2017/11

Reliability:

2 (reliable with restrictions)

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
ECOSAR

2. MODEL (incl. version number)
ECOSAR v1.11

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
O=C(Oc(c(OC)cc(c1)CC=C)c1)C
log Kow: 2.8 (experimental result)

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: short term toxicity to aquatic invertebrates (Daphnid).
- Unambiguous algorithm: Linear regression QSAR; Log 96-h LC50 (mmol/L) = -0.6305 (log Kow) + 0.7049. To convert the LC50 from mmol/L to mg/L, multiply by the molecular weight.
- Defined domain of applicability: Applicable to chemicals with log Kow less than 5.0 and molecular weight less than 1000 g/mol. The model can be suitable for chemicals class of Esters.
- Appropriate measures of goodness-of-fit and robustness and predictivity: N = 40 + 21 and the coefficient of determination R² = 0.7984.
- Mechanistic interpretation: related to the partitioning of the substance from water into the organisms lipid phase.

5. APPLICABILITY DOMAIN
Applicable to chemicals with log Kow less than 5.0 and molecular weight less than 1000 g/mol. The model can be suitable for chemicals class of Esters (monoester).

6. ADEQUACY OF THE RESULT
The substance falls within the applicability domain described above and therefore the predicted value can be considered reliable.
For more information, see Esters SAR document in "Attached background material".

Qualifier:

according to guideline

Guideline:

other: REACH guidance on QSARs R.6, May 2008

Deviations:

no

Principles of method if other than guideline:

See attached QMRF and QPRF.

GLP compliance:

no

Remarks:

(not relevant)

Specific details on test material used for the study:

- log Kow : 2.8 (experimental result)

Details on sampling:

Not applicable

Details on test solutions:

Not applicable

Test organisms (species):

Daphnia sp.

Details on test organisms:

None

Test type:

not specified

Water media type:

not specified

Total exposure duration:

48 h

Remarks on exposure duration:

none

Post exposure observation period:

Not applicable

Hardness:

Not applicable

Test temperature:

Not applicable

pH:

Not applicable

Dissolved oxygen:

Not applicable

Salinity:

Not applicable

Nominal and measured concentrations:

Not applicable

Details on test conditions:

Not applicable

Key result

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

17.942 mg/L

Remarks on result:

other: ECOSAR Class: Esters

Details on results:

See QPRF report

Results with reference substance (positive control):

Not applicable

Reported statistics and error estimates:

N = 40 + 21 and the coefficient of determination R² = 0.7984.

None

Validity criteria fulfilled:

yes

Conclusions:

The substance was predicted to have a LC50 value at 17.942 mg/L to aquatic invertebrates Daphnid after 48h of exposure. The substance falls within the applicability domain and therefore the predicted value can be considered reliable.

Executive summary:

The short term toxicity to daphnid was estimated using the ECOSAR v1.11 QSAR model available from the U.S. EPA.

The estimation 48h-LC50 was 17.942 mg/L (Esters class), calculated from a measured log Kow value at 2.8 and a linear regression:

Log 48h-LC50 (mmol/L) = -0.6305*log Kow + 0.7049

The substance falls within the applicability domain and therefore the predicted value can be considered reliable.

Description of key information

Geometric mean of QSAR models (iSafeRat v1.7 and ECOSAR v1.11):

48h-EC50 = 24.33 mg/L.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

24.33 mg/L

Additional information

To assess the short-term toxicity of the registered substance to aquatic invertebrates, two reliable QSAR results are available.

The first prediction data (KREATiS, 2017) is a QSAR. 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 for the Mode of Action in question (mono and poly-esters MOA). The QSAR model is based on validated data for a training set of 41 mono-esters compounds derived from 48-hour tests on daphnids, for which the concentrations of the test substance had been determined by chemical analyses over the test period. Thewater solubility of the substance given as input was experimentally measured at 410 mg/L. The substance falls within the applicability domain of the model as demonstrated in the QPRF.

The 48-h EC50 based on mobility and measured concentrations was determined to be 33 mg/L with 95%-Confidence Limit between 28 and 39 mg/L.

The second prediction data (ECOSAR, 2017) is also a QSAR. This QSAR prediction used the ECOSAR v1.11 QSAR model available from the U.S. EPA to assess the acute toxicity of the registered substance to daphnids. The substance falls within the applicability domain of the model. The estimation 48h-LC50 was determined at 17.942 mg/L using the chemical class of Esters.

In conclusion, according to these key data points, the key EC50 value on aquatic invertebrates, used for chemical safety assessment, is determined at 24.33 mg/L, corresponding to a geometric mean of predicted EC50 values.