(3aα,4β,7β,7aα)-octahydro-4,7-methano-1H-indene

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:

2017-03-22

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:

QSAR predictions
QSAR based on high quality dataset with very high correlation for the structural group in question. This High accuracy model is therefore considered suitable for use to replace an experimental study as a stand-alone value

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 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:

Not applicable

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
Results from the following species were used in the regression:
Pseudokirchneriella subcapitata, Desmodesmus subspicatus, Scenedesmus quadricauda

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:

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

Salinity:

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 was determined.

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):

no

Remarks:

QSAR model

Key result

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

ca. 0.92 mg/L

Conc. based on:

test mat.

Basis for effect:

growth rate

Remarks on result:

other: 95%CL: 0.29-2.87 mg/L

Details on results:

The test item falls within the applicability domain of the model except for the descriptor domain. From a descriptor domain point of view, the test item falls within the intermediate domain where baseline toxicity cannot be experimentally measured accurately. Moreover the toxicity is likely greater than the water solubility limit. Based on a statistical k-NN approach (k = 3), the predicted toxicity (72h-ErC50) to algae is considered as the geometric mean of the iSafeRat® prediction and the subcooled water solubility limit.

« Intermediate domain » is an area of low solubility where uptake rate is hindered by the poor bioavailability of the molecule in water and therefore equilibrium is not fully reached before the end of the study. This window is between the point where equilibrium is attained and the result fit with the algorithm, and the point where bioavailablity is so low that effects do not occur within the timeframe of the experiment. Thus, an EC50 may be expected to occur for substances found in this solubility window but the results are between the expected algorithms (low EC50 value) and the solubility (maximum EC50 value). In a laboratory, results for substances falling within this window tend to be variable, falling between the upper and lower limit and depends on multiple factors, notably the preparation technique and testing conditions. Therefore, a good approximation of the value likely to be found in a laboratory is achieved using the geometric mean of the algorithm prediction and the water solubility limit.

Results with reference substance (positive control):

Not applicable

Reported statistics and error estimates:

95% CL: 0.29-2.87 mg/L.
QSAR statistical parameters are given in the QMRF and the QPRF

no additionnal informations

Validity criteria fulfilled:

yes

Remarks:

The substance falls within the applicability domains of the QSAR model

Conclusions:

The 72-h ErC50 based on measured concentrations was determined to be 0.92 mg/L with 95%-Confidence Limit between 0.29 and 2.87 mg/L.

Executive summary:

A Quantitative Structure-Activity Relationship (QSAR) was used to calculate the inhibition of growth to algae of the test item (3aR,4R,7R,7aS)-octahydro-1H-4,7-methanoindene. 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" (1), referenced as Method C.3 of Commission Regulation No. 440/2008 (2). 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 validated QSAR model for the Mode of Action (MOA) in question (MoA 1 or MechoA 1.1 i.e. non-polar narcosis). The QSAR model 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 item had been determined by chemical analyses over the test period.

The substance falls within the applicability domain of the model as demonstrated in the QPRF (except for the descriptor domain). The 72-h ErC50 based on measured concentrations was determined to be 0.92mg/L with 95%-Confidence Limit between 0.29 and 2.87 mg/L.

This substance falls within an intermediate zone where the ecotoxicity value of a substance is expected to be between the hypothetical value as predicted by iSafeRat® model and the water solubility value. « Intermediate domain » is an area of low solubility where uptake rate is hindered by the poor bioavailability of the molecule in water and therefore equilibrium is not fully reached before the end of the study. This window is between the point where equilibrium is attained and the result fits with the algorithm, and the point where solubility (and therefore bioavailablity) is so low that effects do not occur within the timeframe of the experiment. Thus, an EC50 may be expected to occur for substances found in this solubility window but the results are between the expected algorithms (low EC50 value) and the solubility (maximum EC50 value).

Description of key information

QSAR model, iSafeRat holistic approach v1.7, key study, validity 1:

72h-ErC50 = 0.92 mg/L (95% CL: 0.29 - 2.87 mg/L).

Key value for chemical safety assessment

EC50 for freshwater algae:

0.92 mg/L

Additional information

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

This value (KREATiS, 2017), assessed as a key datapoint, is a QSAR. A Quantitative Structure-Activity Relationship (QSAR) was used to calculate the inhibition of growth to algae of the test item (3aR,4R,7R,7aS)-octahydro-1H-4,7-methanoindene. 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" (1), referenced as Method C.3 of Commission Regulation No. 440/2008 (2). 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 validated QSAR model for the Mode of Action (MOA) in question (MOA 1 or MechoA 1.1: non-polar narcosis) (Bauer et al., 2018). The QSAR model is based on validated data for a taining set of 40 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 substance falls within the applicability domain of the model as demonstrated in the QPRF (except for the descriptor domain). The 72-h ErC50 based on measured concentrations was determined to be 0.92 mg/L with 95%-Confidence Limit between 0.29 and 2.87 mg/L.

Bauer F., Thomas, P., Fouchard S., Neunlist S., 2018. High-accuracy prediction of mechanisms of action using structural alerts. Computational Toxicology 7:36 -45