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

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Endpoint:

effects on growth of green algae

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 201 (Alga, Growth Inhibition 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 TOXICITY TO ALGAE (72-HOUR ErL50 and NOELr) 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 previously been validated in an internal publication for acute exposure of non-polar narcosis compounds (Bicherel and Thomas, 2014). The algorithm is based on two QSAR models which have been validated to be compliant with the OECD recommandations for QSAR modeling (OECD, 2004, 2007). The QSAR models are based on validated data from a training set of 40 chemicals (for 72-hour ErC50) and 31 chemicals (for NOECr) derived from 72-hour test on algae, for which the concentrations of the test item had been determined by chemical analyses over the test period. Further to this the effective 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: Pseudokirchneriella subcapitata, Desmodesmus subspicatus, Scenedesmus quadricauda

Details on test organisms:

No difference in terms of toxic mechanism of action between algae (or indeed other) aquatic species is expected. Any observed differences may be attributed to lifestyle related parameters and relative duration of study versus cell size 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:

72 h

Remarks on exposure duration:

Results from a test duration of 72 hours only were used for the models.

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:

The QSAR is based on data from studies performed at acceptable pH between 6.0 - 9.0. 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.

Conductivity:

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 measured initial concentration throughout the test) or, if not, the result was based on measured concentrations as geometric mean.

Details on test conditions:

Following 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):

not required

Key result

Duration:

72 h

Dose descriptor:

EL50

Effect conc.:

> 2.7 mg/L

Nominal / measured:

nominal

Conc. based on:

other: loading rate of Water Accomodated Fraction (WAF)

Basis for effect:

growth rate

Remarks on result:

not determinable

Key result

Duration:

72 h

Dose descriptor:

NOELR

Effect conc.:

> 2.7 mg/L

Nominal / measured:

nominal

Conc. based on:

other: loading rate of Water Accomodated Fraction (WAF)

Basis for effect:

growth rate

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.

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

Conclusions:

The TOXICITY TO ALGAE (72-HOUR ErL50 and NOELr) 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 model used to determine their individual TOXICITY TO ALGAE (72-HOUR ErC50 and NOECr). 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 TOXICITY TO ALGAE (72-HOUR ErL50 and NOELr) of the test item tested according to the WAF method was predicted as greater than the solubility limit (2.73 mg/L) for both the 72-HOUR ErL50 and the NOELr.

Executive summary:

A calculation method was used to assess the TOXICITY TO ALGAE (72-HOUR ErL50 and NOELr) 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. 201, "Freshwater Alga and Cyanobacteria, Growth Inhibition Test" (OECD, 2006), referenced as Method C.3 of Commission Regulation No. 440/2008 (European Commission, 2008) adapted for testing of a mixture using the WAF method. The criterions predicted were the Median Effective Loading rate (ErL50), a statistically derived concentration which is expected to cause 50% inhibition of intrinsic rate of growth of the test system and the No Observed Effect Loading rate (NOELr), a tested loading rate which is expected to cause no effect on intrinsic rate of growth of the test system. Both criterions were determined for a period exposure of 72 hours.

 

The TOXICITY TO ALGAE (72-HOUR ErL50 and NOELr) 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 two QSAR models which have been validated to be compliant with the OECD recommandations for QSAR modeling (OECD, 2004, 2007). The QSAR models are based on validated data from a training set of 40 chemicals (for 72-hour ErC50) and 31 chemicals (for NOECr) derived from 72-hour test on algae, for which the concentrations of the test item had been determined by chemical analyses over the test period. Further to this the effective 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 does not completely fall within the applicability domain of the model used to determine their individual TOXICITY TO ALGAE (72-HOUR ErC50 and NOECr). 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 TOXICITY TO ALGAE (72-HOUR ErL50 and NOELr) of the test item tested according to the WAF method was predicted as greater than the solubility limit (2.73 mg/L) for both the 72-HOUR ErL50 and the NOELr.

Description of key information

Calculation method, KREATiS, 2021:  

72h-ErL50 greater than solubility limit  (2.7 mg/L)

72h-NOELr greater than solubility limit  (2.7 mg/L) 

Key value for chemical safety assessment

EC50 for freshwater algae:

2.7 mg/L

EC10 or NOEC for freshwater algae:

2.7 mg/L

Additional information

To assess the toxicity of the registered substance to aquatic algae, two data point are available.

 

Both values (KREATiS, 2021), assessed as key datapoint, are calculation methods.

A calculation method was used to assess the TOXICITY TO ALGAE (72-HOUR ErL50 and NOELr) 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. 201, "Freshwater Alga and Cyanobacteria, Growth Inhibition Test" (OECD, 2006), referenced as Method C.3 of Commission Regulation No. 440/2008 (European Commission, 2008) adapted for testing of a mixture using the WAF method. The criterions predicted were the Median Effective Loading rate (ErL50), a statistically derived concentration which is expected to cause 50% inhibition of intrinsic rate of growth of the test system and the No Observed Effect Loading rate (NOELr), a tested loading rate which is expected to cause no effect on intrinsic rate of growth of the test system. Both criterions were determined for a period exposure of 72 hours.

 

The TOXICITY TO ALGAE (72-HOUR ErL50 and NOELr) 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 two QSAR models which have been validated to be compliant with the OECD recommandations for QSAR modeling (OECD, 2004, 2007). The QSAR models are based on validated data from a training set of 40 chemicals (for 72-hour ErC50) and 31 chemicals (for NOECr) derived from 72-hour test on algae, for which the concentrations of the test item had been determined by chemical analyses over the test period. Further to this the effective 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 does not completely fall within the applicability domain of the model used to determine their individual TOXICITY TO ALGAE (72-HOUR ErC50 and NOECr). 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 TOXICITY TO ALGAE (72-HOUR ErL50 and NOELr) of the test item tested according to the WAF method was predicted as greater than the solubility limit (2.7 mg/L) for both the 72-HOUR ErL50 and the NOELr.