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

Long-term toxicity to fish

Link to relevant study record(s)

Reference

Endpoint:

fish early-life stage toxicity

Type of information:

mixture rules calculation

Adequacy of study:

key study

Study period:

From 02 November 2021 to 22 november 2022

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 210 (Fish, Early-Life Stage Toxicity Test)

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 CHRONIC TOXICITY TO FISH (32-DAY EL10) 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 is an extension of the method 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 27 chemicals derived from 32-day 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 non-bioavailable fraction.

GLP compliance:

no

Remarks:

(calculation method)

Analytical monitoring:

no

Details on sampling:

not applicable

Vehicle:

no

Details on test solutions:

not applicable

Test organisms (species):

other: Danio rerio, Pimephales promelas, Cyprinus carpio, Oncorhynchus mykiss

Details on test organisms:

Results from the following species were used in the regression:
Danio rerio, Pimephales promelas, Cyprinus carpio, Oncorhynchus mykiss

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: calculation method based on QSAR model predictions

Water media type:

freshwater

Limit test:

no

Total exposure duration:

32 d

Remarks on exposure duration:

Results from a test duration of 32 to 102 days were included. Equilibrium between organisms and external medium was expected to be equivalent from 32 days.

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 10 to 25 °C depending on the fish species used to construct the algorithm.

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

Conductivity:

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. maintained within ± 20 % of the nominal) or, if not, the result was based on measured concentrations as geometric mean.

Details on test conditions:

Preferentially results from a flow-through test were used. However semi-static with daily renewal of test solutions and the control 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.

Reference substance (positive control):

not required

Key result

Duration:

32 d

Dose descriptor:

EC10

Effect conc.:

0.46 mg/L

Nominal / measured:

nominal

Conc. based on:

other: loading rate of Water Accomodated Fraction (WAF)

Basis for effect:

other: calculation method

Remarks on result:

not determinable

Details on results:

The test item falls within the applicability domain of the model and can therefore be considered a reliable prediction for chronic toxicity (32d-EC10) to fish. Therefore, this endpoint value can be considered valid for use in risk assessment and classification and labelling.

Results with reference substance (positive control):

not applicable

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

Remarks:

The test item falls within the applicability domain of the model and can therefore be considered a reliably prediction for chronic toxicity (32d-EC10) to fish.

Conclusions:

The CHRONIC TOXICITY TO FISH (32-DAY EL10) 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 falls within the applicability domain of the QSAR model used to determine their individual CHRONIC TOXICITY TO FISH (32-DAY EC10). Moreover, 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 CHRONIC TOXICITY TO FISH (32-DAY EL10) of the test item tested according to the WAF method was predicted as a loading rate of 4.6E-01 mg/L.

Executive summary:

A calculation method prediction was used to assess the CHRONIC TOXICITY TO FISH (32-DAY EL10) 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. 210, "Fish, Earlylife Stage Toxicity Test" (OECD, 2013) adapted for testing of a mixture using the WAF method. The criterion predicted was the EL10 (10% Effective Loading rate of the mixture), a statistically derived loading rate which is expected to cause an effect of 10% on growth or reproducibility within a period of 32 days.

 

The CHRONIC TOXICITY TO FISH (32-DAY EL10) 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 is an extension of the method 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 27 chemicals derived from 32-day 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 non-bioavailable fraction.

Each constituent of the test item falls within the applicability domain of the QSAR model used to determine their individual CHRONIC TOXICITY TO FISH (32-DAY EC10). Moreover, 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 CHRONIC TOXICITY TO FISH (32-DAY EL10) of the test item tested according to the WAF method was predicted as a loading rate of 4.6E-01 mg/L.

Description of key information

Calculation method, Kreatis, 2021

32d-EL10 = 0.46 mg/L 

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Dose descriptor:

EC10

Effect concentration:

0.46 mg/L

Additional information

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

 

This value (QSAR-KREATiS, 2020) is assessed as a key datapoint and is a calculation method. This calculation method prediction was used to assess the CHRONIC TOXICITY TO FISH (32-DAY EL10) 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. 210, "Fish, Earlylife Stage Toxicity Test" (OECD, 2013) adapted for testing of a mixture using the WAF method. The criterion predicted was the EL10 (10% Effective Loading rate of the mixture), a statistically derived loading rate which is expected to cause an effect of 10% on growth or reproducibility within a period of 32 days.

 

The CHRONIC TOXICITY TO FISH (32-DAY EL10) 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 is an extension of the method 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 27 chemicals derived from 32-day 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 non-bioavailable fraction.

Each constituent of the test item falls within the applicability domain of the QSAR model. Moreover, 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 CHRONIC TOXICITY TO FISH (32-DAY EL10) of the test item tested according to the WAF method was predicted as a loading rate of 4.6E-01 mg/L.