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

Short-term toxicity to fish

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to fish

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 203 (Fish, Acute Toxicity Test)

Deviations:

not applicable

Remarks:

(QSAR model)

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method C.1 (Acute Toxicity for Fish)

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 fish as would be expected in a laboratory experiment following the OECD Guideline 203 (2) and EC method C.1 (3) for specific named modes of action. The model provides an in silico prediction for the 96-hour LC50 value that can effectively be used in place of an experimentally derived 96-hour LC50 value. The regression based method used to achieve this has been fully validated following the OECD (2004) (1) recommendations.

GLP compliance:

no

Specific details on test material used for the study:

Not applicable

Analytical monitoring:

no

Details on sampling:

Not applicable

Details on test solutions:

Not applicable

Test organisms (species):

other: Danio rerio, Oncorhynchus mykiss, Lepomis macrochirus, Pimephales promelas,Oryzias latipes, Leuciscus idus

Details on test organisms:

Results from the following species were used in the regression:
Danio rerio, Oncorhynchus mykiss, Lepomis macrochirus, Pimephales promelas,Oryzias latipes, Leuciscus idus
No difference in terms of toxic mechanism of action between fish freshwater species is expected. Any observed differences may be attributed to lifestyle related parameters (e.g. relative differences in storage lipid content between species) 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:

96 h

Remarks on exposure duration:

Only results from a test duration of 96 hours were included.

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 14 to 25 °C depending on the fish species used to construct the algorithm. While it is recognized that this may contribute to some extent to the variability of the LC50 values found in experimental data, KREATiS has not observed a clear trend suggesting that normalization to temperature would necessarily improve the algorithm (say for trout as opposed to warm water species like fathead minnow for example) for monoconstituents. Nevertheless, this is a recognized area for further research by KREATiS.

pH:

Test results were taken from studies with measured pHs between 6.0 - 8.5.

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 sufficient evidence was presented to determine that the substance 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:

A variety of test designs were accepted: Preferentially results from semi-static experiments with daily renewal of test solutions and the control or from flow-through tests were used. However, for stable, low volatility substances a static design was accepted (preferably accompanied by analytical measurements over the study period). For suspected volatile substances only tests performed in closed vessels were accepted unless accompanying analytical monitoring proved such a design was not necessary.
The studies used in the dataset were considered valid under the OECD guideline and REACH regulation (REACH, 2006) (7) (i.e. Klimisch score 1 or 2) by registrants of the substances included in the training and test sets were revalidated by KREATiS and the critical parameters of the study were considered to be within acceptable limits.

Reference substance (positive control):

no

Remarks:

(QSAR model)

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

0.87 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Remarks on result:

other: 95% CL: 0.26-2.9%

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. Based on a k-NN approach (with k = 3), the toxicity of the test item is estimated as the geometric mean between the toxicity value predicted using the regression line and the solubility cut-off line (with the confidence intervals being placed at these limits).
The 96h-LC50 of the test item to fish was predicted as 0.87 mg/L.

Results with reference substance (positive control):

Not applicable

Reported statistics and error estimates:

95% confidence interval (α = 0.05): 0.26 – 2.9 mg/L.
QSAR statistical parameters are given in the QMRF and the QPRF

Sublethal observations / clinical signs:

No additional information

Validity criteria fulfilled:

yes

Remarks:

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

Conclusions:

The 96-h LC50 of THDCPD based on mortality and measured concentrations was determined to be 0.87 mg/L with 95%-Confidence Limit between 0.26 and 2.9 mg/L.

Executive summary:

A Quantitative Structure Activity Realtionship (QSAR) model was used to calculate the acute toxicity to fish exposed to 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 the Guideline for Testing of Chemicals No. 203, "Fish Acute Toxicity Test" , referenced as Method C.1 of Commission Regulation No. 440/2008 . The criterion predicted was the LC50 (Median Lethal Concentration), a statistically derived concentration which is expected to cause mortality in 50% of test animals within a period of 96 hours.

The acute toxicity to fish was determined using a validated QSAR for the Mechanism of Action (MechoA) in question (MechoA 1.1, i.e. non-polar narcosis) (Bauer et al. 2018). The QSAR is based on validated data for a training set of 67 chemicals derived from 96-hour test on fish, for which the concentrations of the test item had been determined by chemical analyses over the test period.

The result below is the toxicity value anticipated during a 96-hour LC50 study on fish based on measured concentrations. The 96-hour LC50 of THDCPD based on mortality and measured concentrations was determined to be 0.87 mg/K with 95%-Confidence Limit between 0.26 and 2.9 mg/L.

Description of key information

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

96h-LC50 = 0.87 mg/L (95% CL: 0.26 - 2.9 mg/L).

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

0.87 mg/L

Additional information

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

This value (KREATiS, 2018), assessed as a key datapoint, is a QSAR: A Quantitative Structure Activity Realtionship (QSAR) model was used to calculate the acute toxicity to fish exposed to 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 the Guideline for Testing of Chemicals No. 203, "Fish Acute Toxicity Test", referenced as Method C.1 of Commission Regulation No. 440/2008. The criterion predicted was the LC50 (Median Lethal Concentration), a statistically derived concentration which is expected to cause mortality in 50% of test animals within a period of 96 hours.

The acute toxicity to fish was determined using a validated QSAR for the Mechanism of Action (MechoA) in question (MechoA 1.1, i.e. non-polar narcosis) (Bauer et al., 2018). The QSAR is based on validated data for a training set of 67 chemicals derived from 96-hour test on fish, for which the concentrations of the test item had been determined by chemical analyses over the test period.

The result below is the toxicity value anticipated during a 96-hour LC50 study on fish based on measured concentrations. The 96-hour LC50 of THDCPD based on mortality and measured concentrations was determined to be 0.87 mg/K with 95%-Confidence Limit between 0.26 and 2.9 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