Reaction mass of (3aR*,5aS*,9aS*,9bR*)-3a,6,6,9a-Tetramethyldodecahydronaphtho[2,1-b]furan and (3aR*,5aS*,9aS*,9bS*)-3a,6,6,9a-Tetramethyldodecahydronaphtho[2,1-b]furan

Short-term toxicity to fish

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to fish

Type of information:

mixture rules calculation

Adequacy of study:

key study

Study period:

From 02 November 2021 to 22 November 2021

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Remarks:

Each constituent of the test item does not completely fall within the applicability domain of the QSAR model used to determine their individual ACUTE TOXICITY TO FISH (96-HOUR LC50). Their toxicity values were extrapolated.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 203 (Fish, Acute Toxicity Test)

Deviations:

yes

Remarks:

(tested according to the Water Accommodated Fraction (WAF) approach, i.e. OECD technical guideline 23)

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method C.1 (Acute Toxicity for Fish)

Deviations:

yes

Remarks:

(tested according to the Water Accommodated Fraction (WAF) approach, i.e. OECD technical guideline 23)

Principles of method if other than guideline:

The ACUTE TOXICITY TO FISH (96-HOUR LL50) was determined using iSafeRat® calculation method adapted for a mixture of compounds with the Mechanism of Action (MechoA) in question (MechoA 1.1, i.e. non-polar narcosis) (Bauer et al., 2018). This method has been published for acute exposure of non-polar narcosis compounds (Bicherel and Thomas, 2021). The algorithm is based on a QSAR model which has been validated to be compliant with the OECD recommandations for QSAR modeling (OECD, 2004, 2007). The QSAR model 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. Further to this the lethal loading rate of the WAF is determined by using a series of calculation steps using phase equilibrium thermodynamics and excluding the nonbioavailable fraction, this approach is based on validated data derived from 96-hour tests on fish, for which the concentrations of the test item had been determined by chemical analyses over the test period.

GLP compliance:

no

Remarks:

Calculation method

Specific details on test material used for the study:

Predicted Subcooled liquid Water Solubility : 2.32 mg/L at 25 °C (Kreatis, 2021)
Melting point: 65°C (Lange 2015)
Log Kow : 5.09 at 25°C (Firmenich, 2013)

Analytical monitoring:

no

Details on sampling:

Not applicable

Vehicle:

no

Details on test solutions:

Not applicable

Test organisms (species):

not specified

Test type:

other: Calculation method based on QSAR model predictions

Water media type:

freshwater

Limit test:

no

Total exposure duration:

96 h

Hardness:

The QSAR model 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:

Test results were taken from studies with measured pHs between 6 - 9.

Dissolved oxygen:

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

Salinity:

Not applicable

Nominal and measured concentrations:

Studies were used for QSAR model development 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:

Studies with various test designs were selected for QSAR model development. Preferentially results from semi-static studies were used. However, substances tested using a static design were 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.

Reference substance (positive control):

not required

Remarks:

Calculation method

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

2.73 mg/L

Nominal / measured:

nominal

Conc. based on:

other: loading rate of Water Accomodated Fraction (WAF)

Basis for effect:

mortality (fish)

Remarks on result:

not determinable

Details on results:

Using a loading rate of 2.73 mg/L, i.e. at the maximal solubility of the test item in water, and after removal of the nonbioavailable fraction, the remaining solubilised fraction is not sufficient to exert any toxicity effect. Therefore it is not possible to determine a toxic value below the water solubility limit.
The result below is the anticipated toxicity value during a 96-hour LL50 study on fish based on the typical compositionof the test item. The 96-hour LL50 is calculated as follows:
Composition Time (h) LL50 (mg test item/L)
typical 96 > solubility limit

Results with reference substance (positive control):

Not applicable

Sublethal observations / clinical signs:

Prior Analysis of the MechoA constituents of the test item.

The calculation method used in this study is based on toxic additivity principle. That means the toxic parts of each constituent are added up. Therefore the constituents considered within the mixture should act with a similar MechoA. The MechoA of the consituents are determined using the methodology described by Bauer et al. (2018) and reported in the Table below.

 

MechoA of the constituents.

Constituents	MechoA	Description
Isomer 1	1.1	non-polar narcotic
Isomer 2	1.1	non-polar narcotic
Isomer 3	1.1	non-polar narcotic

Since the constituents of the test item act with the same general MechoA, the calculation method is directly applicable

Validity criteria fulfilled:

yes

Conclusions:

The ACUTE TOXICITY TO FISH (96-HOUR LL50) of the test item has been determined using the iSafeRat® calculation method for mixtures tested according to the Water Accomodated Fraction (WAF) approach. Each constituent of the test item does not completely fall within the applicability domain of the QSAR model used to determine their individual ACUTE TOXICITY TO FISH (96-HOUR LC50). Their toxicity values were extrapolated.
However, each constituent of the test item acts with the same general MechoA. Therefore the calculation method is directly applicable and the final result for the test item can be considered valid for use in risk assessment and classification and labelling. Therefore, the final result for the test item is considered as an extrapolation (reliable with restrictions). The result remains valid for use in risk assessment and classification and labelling. The ACUTE TOXICITY TO FISH (96-HOUR LL50) of the test item tested according to the WAF method was redicted as greater than the solubility limit.

Executive summary:

A calculation method prediction was used to assess the ACUTE TOXICITY TO FISH (96-HOUR LL50) of the test item, a multiconstituent substance, tested according to the Water Accommodated Fraction (WAF) approach. This calculation method 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" (OECD, 2019), referenced as Method C.1 of Commission Regulation No. 440/2008 (European Commission, 2008) adapted for testing of a mixture using the WAF method. 

 

The ACUTE TOXICITY TO FISH (96-HOUR LL50) was determined using iSafeRat® calculation method adapted for a mixture of compounds with the Mechanism of Action (MechoA) in question (MechoA 1.1, i.e. non-polar narcosis) (Bauer et al., 2018). This method has been published for acute exposure of non-polar narcosis compounds (Bicherel and Thomas, 2021). The algorithm is based on a QSAR model which has been validated to be compliant with the OECD recommandations for QSAR modeling (OECD, 2004, 2007). The QSAR model 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. Further to this the lethal loading rate of the WAF is determined by using a series of calculation steps using phase equilibrium thermodynamics and excluding the nonbioavailable fraction, this approach is based on validated data derived from 96-hour tests on fish, for which the concentrations of the test item had been determined by chemical analyses over the test period.

 

 Each constituent of the test item does not completely fall within the applicability domain of the QSAR model used to determine their individual ACUTE TOXICITY TO FISH (96-HOUR LC50). Their toxicity values were extrapolated.
However, each constituent of the test item acts with the same general MechoA. Therefore the calculation method is directly applicable and the final result for the test item can be considered valid for use in risk assessment and classification and labelling. Therefore, the final result for the test item is considered as an extrapolation (reliable with restrictions). The result remains valid for use in risk assessment and classification and labelling.

The criterion predicted was the median lethal loading rate of the mixture LL50 (Median Lethal Loading), a statistically derived loading rate which is expected to cause mortality in 50% of test animals within a period of 96 hours
The ACUTE TOXICITY TO FISH (96-HOUR LL50) of the test item tested according to the WAF method was predicted as greater than the solubility limit.

Description of key information

calculation method, KREATiS 2021

96h-LL50 greater than the solubility limit (2.7 mg/L )

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Effect concentration:

> 2.7 mg/L

Additional information

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

 

This value (KREATiS, 2021) is assessed as a key datapoint This calculation method prediction (iSafeRat  v1.9) was performed on the registered substance, to assess the acute toxicity of the substance to fish.

A calculation method prediction was used to assess the ACUTE TOXICITY TO FISH (96-HOUR LL50) of the test item, a multiconstituent substance, tested according to the Water Accommodated Fraction (WAF) approach. This calculation method 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" (OECD, 2019), referenced as Method C.1 of Commission Regulation No. 440/2008 (European Commission, 2008) adapted for testing of a mixture using the WAF method. 

 

The ACUTE TOXICITY TO FISH (96-HOUR LL50) was determined using iSafeRat® calculation method adapted for a mixture of compounds with the Mechanism of Action (MechoA) in question (MechoA 1.1, i.e. non-polar narcosis) (Bauer et al., 2018). This method has been published for acute exposure of non-polar narcosis compounds (Bicherel and Thomas, 2021). The algorithm is based on a QSAR model which has been validated to be compliant with the OECD recommandations for QSAR modeling (OECD, 2004, 2007). The QSAR model 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. Further to this the lethal loading rate of the WAF is determined by using a series of calculation steps using phase equilibrium thermodynamics and excluding the nonbioavailable fraction, this approach is based on validated data derived from 96-hour tests on fish, for which the concentrations of the test item had been determined by chemical analyses over the test period.

 

 Each constituent of the test item does not completely fall within the applicability domain of the QSAR model used to determine their individual ACUTE TOXICITY TO FISH (96-HOUR LC50). Their toxicity values were extrapolated.
However, each constituent of the test item acts with the same general MechoA. Therefore the calculation method is directly applicable and the final result for the test item can be considered valid for use in risk assessment and classification and labelling. Therefore, the final result for the test item is considered as an extrapolation (reliable with restrictions). The result remains valid for use in risk assessment and classification and labelling.

The criterion predicted was the median lethal loading rate of the mixture LL50 (Median Lethal Loading), a statistically derived loading rate which is expected to cause mortality in 50% of test animals within a period of 96 hours
The ACUTE TOXICITY TO FISH (96-HOUR LL50) of the test item tested according to the WAF method was predicted as greater than the solubility limit.