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

Toxicity to microorganisms

Link to relevant study record(s)

Reference

Endpoint:

activated sludge respiration inhibition testing

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

04/12/2018

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:

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 209 (Activated Sludge, Respiration Inhibition Test

Deviations:

not applicable

Remarks:

(QSAR model)

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method C.11 (Biodegradation: Activated Sludge Respiration 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 microorganisms as would be expected in a laboratory experiment following OECD Guideline 209 and EC method C.11 for specific named mechanism of action.
The model provides an in silico prediction for the 30 to 180 miutes EC50 value that can effectively be used in place of an experimentally derived 30 to 180 miutes EC50 value. The regression based method used to achieve this has been fully validated following the OECD (2004) recommendations.

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):

activated sludge

Details on inoculum:

This study is not performed on a single or known species as such. Results were acquired from studies where the following test system was used:Activated sludge collected and treated according to the method outlined in OECD 209

Test type:

static

Water media type:

freshwater

Limit test:

no

Total exposure duration:

180 min

Remarks on exposure duration:

Results from a test duration of 30 to 180 minutes only were used for this algorithm.

Post exposure observation period:

None

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 studies 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:

No data

Salinity:

Not applicable

Nominal and measured concentrations:

Studies were used only where sufficient evidence was presented to determine that the stubstance was stable under test conditions (i.e. maintened within ± 20 % of the nominal) or, if not, the result was based on measured concentrations as geometric mean.

Details on test conditions:

Following OECD 209, all studies used 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:

180 min

Dose descriptor:

EC50

Effect conc.:

> 2.87 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

inhibition of total respiration

Remarks on result:

other: 95% CL: not applicable

Details on results:

The water solubility value given as input to the iSafeRat® ASRIT HA-QSAR model do not fall within the descriptor domain of the model between log water solubility (in log (mol/L)) of -2.72 to 1.01 where the EC50 can be calculated. Moreover it falls beyond the log water solubility (in log (mol/L)) of -3.005 where the EC50 is considered as greater than the subcooled liquid water solubility value within the exposure period of the test.

Results with reference substance (positive control):

Not applicable

Reported statistics and error estimates:

QSAR statistical parameters are given in the QMRF and the QPRF

No additional information

Validity criteria fulfilled:

yes

Remarks:

The substance falls within the domain of the model except for the descriptor domain.

Conclusions:

The 30-180min EC50 of THDCPD to activated sludge is greater than the subcooled liquid water solubility value within the exposure period of the test.

Executive summary:

A Quantitative Structure-Activity Relationship (QSAR) model was used to calculate the inhibition of respiration to activated sludge of the test item (3aα,4β,7β,7aα)-octahydro-4,7-methano-1H-indene. 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 Guideline for Testing of Chemicals No. 209, "Activated Sludge, Respiration Inhibition Test (Carbon and Ammonium Oxidation)", referenced as Method C.11 of Commission Regulation No. 440/2008. The criterion predicted was the 30 to 180 minutes EC50 (Median Effective Concentration for specific respiration rate), a statistically derived concentration which is expected to cause 50% inhibition of intrinsic rate of respiration of the test system within a period of 30 to 180 minutes as an effect on the organic carbon oxidation process. The results from this study do not include the supplementary test results that may be required to determine the effect on nitrification. It should be noted that a specific test duration time could not be determined for this model as 30 and 180

minute data were available but not in sufficient quantity to separate them into two separate models.

The respiration inhibition of activated sludge was determined using a validated QSAR model for the Mechanism of Action (MechoA) in question (MOA1=MechoA 1.1, i.e. non-polar narcosis).The QSAR model is based on validated data for a training set of 12 chemicals derived from 30-180 minute EC50 for which the concentrations of the test item had been determined by chemical analyses over the test period. Further valid data were available but the values were all above the water solubility of the substance and were therefore not included as part of the regression. On the other hand, these data could be used to determine the point at which the regression no longer holds true and results from experimental studies on this MOA are expected to be greater than the solubility limit (i.e. test substance concentrations up to 100 mg/L will result in no effect on activated sludge respiration).

The 30-180min EC50 of THDCPD to activated sludge is greater than the subcooled liquid water solubility value within the exposure period of the test.

The test item falls within the domain of the model except for the descriptor domain. It falls beyond the limit of water solubility where the toxicity value is expected to be greater than the water solubility value within the exposure period of the test. This endpoint result can be considered valid for use in risk assessment and classification and labelling.

Description of key information

QSAR model, iSafeRat holistic approach v1.8, key study, validity 1:

EC50 (30 -180min)> water solubility (95% CL: not applicable).

Additional information

One valid key study is available to assess the acute microbial toxicity of the registered substance,THDCPD:

A Quantitative Structure-Activity Relationship (QSAR) model was used to calculate the inhibition of respiration to activated sludge of the test item (3aα,4β,7β,7aα)-octahydro-4,7-methano-1H-indene. 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 Guideline for Testing of Chemicals No. 209, "Activated Sludge, Respiration Inhibition Test (Carbon and Ammonium Oxidation)", referenced as Method C.11 of Commission Regulation No. 440/2008. The criterion predicted was the 30 to 180 minutes EC50 (Median Effective Concentration for specific respiration rate), a statistically derived concentration which is expected to cause 50% inhibition of intrinsic rate of respiration of the test system within a period of 30 to 180 minutes as an effect on the organic carbon oxidation process. The results from this study do not include the supplementary test results that may be required to determine the effect on nitrification. It should be noted that a specific test duration time could not be determined for this model as 30 and 180

minute data were available but not in sufficient quantity to separate them into two separate models.

The respiration inhibition of activated sludge was determined using a validated QSAR model for the Mechanism of Action (MechoA) in question (MoA1=MechoA 1.1, i.e. non-polar narcosis) (Bauer et al., 2018).The QSAR model is based on validated data for a training set of 12 chemicals derived from 30-180 minute EC50 for which the concentrations of the test item had been determined by chemical analyses over the test period. Further valid data were available but the values were all above the water solubility of the substance and were therefore not included as part of the regression. On the other hand, these data could be used to determine the point at which the regression no longer holds true and results from experimental studies on this MOA are expected to be greater than the solubility limit (i.e. test substance concentrations up to 100 mg/L will result in no effect on activated sludge respiration).

The 30-180min EC50 of THDCPD to activated sludge is greater than the subcooled liquid water solubility value within the exposure period of the test.

The test item falls within the domain of the model except for the descriptor domain. It falls beyond the limit of water solubility where the toxicity value is expected to be greater than the water solubility value within the exposure period of the test. This endpoint result can be considered valid for use in risk assessment and classification and labelling.

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