(E)-1-(2,6,6-trimethyl-2-cyclohexen-1-yl)-2-buten-1-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:

From 2015-07-27 to 2015-07-28

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

Remarks:

QSAR value. The substance falls into the applicability domain of the model QSAR.

Justification for type of information:

1. SOFTWARE
iSafeRat® HA-QSAR

2. MODEL (incl. version number)
iSafeRat® holistic HA-QSAR v1.4

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CC=CC(=O)C1C(C)=CCCC1(C)C
Experimental Log Kow value (slow-stirring method): 3.66 (25°C, pH 5.83)

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

5. APPLICABILITY DOMAIN
See attached QMRF

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)

Principles of method if other than guideline:

The acute toxicity to aquatic algae was determined using a validated QSAR for the Mode of Action in question, based on validated data derived from 72-hour ErC50 tests on algae, for which the concentrations of the test item had been determined by chemical analyses over the test period. The QSAR is a simple linear regression of sub-cooled liquid solubility versus 72-h ErC50 for algae and is valid within the applicability domain defined in the QMRF.

GLP compliance:

no

Specific details on test material used for the study:

- Physical state: liquid
- Mode of action: Non-polar narcotic (MOA 1)
- Experimental Log Kow value (slow-stirring method): 3.66 (25°C, pH 5.83)

Analytical monitoring:

no

Details on sampling:

Not applicable

Vehicle:

no

Details on test solutions:

Not applicable

Test organisms (species):

other: algae spp.

Details on test organisms:

Not applicable

Test type:

other: QSAR method

Water media type:

freshwater

Limit test:

no

Total exposure duration:

72 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 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:

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

Following 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):

no

Remarks:

QSAR model

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

5 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

growth rate

Remarks on result:

other: 95% CL: 4.3-5.7 mg/L

Details on results:

The predicted value is reliable since the test substance falls within the applicability domain of the model. The water solubility value of the test substance is within descriptor domain of the model between log water solubility (in log(mol/L)) of -4.38 to 0.49. Moreover the test substance is attributed to the class of non-polar narcotic compounds (MOA 1).

Results with reference substance (positive control):

Not applicable

Reported statistics and error estimates:

95% CL: 4.3-5.7 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 applicability domains of the QSAR model

Conclusions:

The 72-h ErC50 based on measured concentrations was determined to be 5.0 mg/L with 95%-Confidence Limit between 4.3 and 5.7 mg/L.

Executive summary:

A QSAR prediction (KREATiS, 2015) 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 Mode of Action in question, (MOA 1, non-polar narcosis). Use of this MOA for substituted α,β-unsaturated ketones has previously been demonstrated as acceptable in a position paper (KREATiS, 2015; in "Attached background material"). 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 of the substance given as input was derived from the experimental log Kow value, measured at 3.66 with a slow-stirring method.

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 5.0 mg/L with 95%-Confidence Limit between 4.3 and 5.7 mg/L.

Description of key information

QSAR model, iSafeRat holistic approach v1.4, key study, validity 1:

72h-ErC50 = 5.0 mg/L (95% CL: 4.3-5.7 mg/L).

Key value for chemical safety assessment

EC50 for freshwater algae:

5 mg/L

Additional information

To assess the toxicity of the registered substance to aquatic algae, one data point is available.

This value (KREATiS, 2015), assessed as a key datapoint, is a QSAR. This QSAR prediction (iSafeRat holistic approach v1.4) was performed on the registered substance, to assess the inhibition of growth to algae of the 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 growth inhibition of algae was determined using a validated QSAR for the Mode of Action in question, (MOA 1, non-polar narcosis). Use of this MOA for substituted α,β-unsaturated ketones has previously been demonstrated as acceptable in a position paper (KREATiS, 2015; available in the Endpoint Study Record). This QSAR is based on validated data for a training set of 40 chemicals derived from 72-hour ErC50 tests on algae, 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 derived from the experimental log Kow value, measured at 3.66 with a slow-stirring method. The substance falls within the applicability domain of the model. The 72 -h ErC50 based on growth rate was determined to be 5.0 mg/L (95%-Confidence Limit: 4.3 -5.7 mg/L).

In conclusion, as the same QSAR model was validated for the "short-term toxicity to aquatic invertebrates" endpoint with an experimental study and the results from this prediction was observed to be similar to those obtained from the experimental study, considering the biological and experimental variabilities, this result can be used with high reliability. Therefore, the 72h-ErC50 value on algae was considered to be 5.0 mg/L (95% CL: 4.3 -5.7 mg/L).