Marjoram, sweet, ext.

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

calculation (if not (Q)SAR)

Remarks:

Estimated by calculation

Adequacy of study:

key study

Study period:

2018-03-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

accepted calculation method

Remarks:

Calculation method is used ; calculation method applicable for the endpoint

Justification for type of information:

See attached documents for full details

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Deviations:

yes

Remarks:

calculation method

Principles of method if other than guideline:

The first step of the iSafeRat mixture toxicity calculation employs phase equilibrium thermodynamics in order to determine the concentrations of each constituent within the WAF. This fraction equates to the analyzable fraction of a WAF study.
Within the WAF, the constituents also partition between themselves further reducing the bioavailable fraction and thus the toxicity of the mixture compared to the individual constituents. In the calculation the second step is to remove this non-bioavailable fraction.
The final step is to determine the truly bioavailable fraction of the WAF per constituent. The EC50s of each constituent are predicted using the iSafeRat QSAR model. An additivity approach (based on Chemical Activity of each constituent) is used in order to calculate the Effective Loading rate of the WAF.
The method has been validated using data derived from 48-hour EC50 tests on aquatic invertebrates, 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

Specific details on test material used for the study:

None

Analytical monitoring:

no

Details on sampling:

not applicable

Vehicle:

no

Details on test solutions:

not applicable

Test organisms (species):

Daphnia magna

Details on test organisms:

not applicable

Test type:

other: calculation method

Water media type:

freshwater

Limit test:

no

Total exposure duration:

48 h

Remarks on exposure duration:

48h-EL50 (effective loading rate of WAF)

Post exposure observation period:

not applicable

Hardness:

Hardness is not a necessary component of the WAF calculation

Test temperature:

The Temperature is not a necessary component of the WAF calculation.

pH:

The pH is not a necessary component of the WAF calculation

Dissolved oxygen:

The oxygen concentration is not a necessary component of the WAF calculation

Salinity:

Salinity is not a necessary component of the WAF calculation.

Nominal and measured concentrations:

The calculation determines measured concentrations

Details on test conditions:

calculation method

Reference substance (positive control):

not required

Key result

Duration:

48 h

Dose descriptor:

EL50

Effect conc.:

5.8 mg/L

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: Based on typical composition

Details on results:

not applicable

Results with reference substance (positive control):

not applicable

Reported statistics and error estimates:

not applicable

Determination of the Analytically Measurable Aqueous Phase (AMAP).

Using the model, the specific concentration of each constituent in the WAF can be accurately determined at any loading rate taking into account the original composition of the mixture and the new corrected limit of solubility of each constituent. The sum of these concentrations, the AMAP, is equivalent to the concentration of all constituents that would be measured in a WAF test. For a given loading rate, the loaded concentration of each constituent is compared to its respective solubility limit. If one is higher than the solubility limit then it is considered that the concentration of the constituent will be equal to its solubility limit. If lower, the true loading concentration is considered. Provided this adapted water solubility limits for each consitutents. Analytically measurable concentrations in aqueous solutions expected from known WAF loading rates of characterised mixtures can be calculated.

At this 48-hour EL50 the expected concentrations of each constituent in the mixture (based on thermodynamic calculation) are as follows:

Analytically Measured Aqueous Phase (AMAP) calculated at the predicted EL₅₀.

constituents	concentration in the WAF (mg.L^-1)
constituent 1	0.84
constituent 2	0.77
constituent 3	0.76
constituent 4	0.011
constituent 5	0.53
constituent 6	0.50
constituent 7	0.19
constituent 8	0.19
constituent 9	0.19
constituent 10	0.14
constituent 11	0.12
constituent 12	0.11
constituent 13	0.088
constituent 14	0.00069
constituent 15	0.061
constituent 16	0.056

 

Validity criteria fulfilled:

yes

Conclusions:

The following toxicity value has been predicted for the registered substance: 48h-EL50 = 5.8 mg/L

Executive summary:

The acute toxicity of the registered substance to aquatic invertebrates has been investigated using an in-house calculation method that replaces an OECD 202 study and guideline for Testing of Chemicals No. 23 (i.e. WAF conditions). The typical composition has been investigated.

 

The first step of the iSafeRat mixture toxicity calculation employs phase equilibrium thermodynamics in order to determine the concentrations of each constituent within the WAF. This fraction equates to the analysable fraction of a WAF study. In the calculation the second step is to remove this non-bioavailable fraction. Within the WAF, the constituents also partition between themselves further reducing the bioavailable fraction and thus the toxicity of the mixture compared to the individual constituents.These two reasons explain why ecotoxicity values from WAF studies are always higher for non-polar narcotic mixtures than the calculated values from CLP additivity calculation.

The final step is to determine the truly bioavailable fraction of the WAF per constituent. The EC50s of each constituent were predicted using the iSafeRat QSAR model (and QPRF as well as the QMRF are provided). An additivity approach (based on Chemical Activity of each constituent) is used in order to calculate the Effective Loading rate of the WAF.

The 48-h EL50 was predicted to be 5.8 mg test material/L.

Description of key information

The following toxicity value has been estimated for the registered substance: 48h-EL50 = 5.8 mg test item/L

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

5.8 mg/L

Additional information

For that endpoint, one reliable study was available: an in-house calculation method that replaces an OECD 202 study and guideline for Testing of Chemicals No. 23 (i.e. WAF conditions). A typical composition of the substance has been investigated. The algorithm used for the purpose of this study is based on a QSAR model which has been validated to be compliant with the OECD recommendations for QSAR modeling (OECD, 2004).

 

The first step of the iSafeRat mixture toxicity calculation employs phase equilibrium thermodynamics in order to determine the concentrations of each constituent within the WAF. This fraction equates to the analysable fraction of a WAF study. In the calculation the second step is to remove this non-bioavailable fraction. Within the WAF, the constituents also partition between themselves further reducing the bioavailable fraction and thus the toxicity of the mixture compared to the individual constituents.

These two reasons explain why ecotoxicity values from WAF studies are always higher for non-polar narcotic mixtures than the calculated values from CLP additivity calculation.The final step is to determine the truly bioavailable fraction of the WAF per constituent. The EC50s of each constituent were predicted using the iSafeRat QSAR model (see table below) and the QMRF/QPRF have been attached to the dossier.

Then, an additivity approach (based on Chemical Activity of each constituent) is used in order to calculate the Effective Loading rate of the WAF.

The results below are the anticipated acute toxicity value anticipated during a 48-hour EL₅₀ study on daphnids based on the WAF method. The 48-hour EL₅₀ is calculated as follows:

 

Composition	Time (h)	EL50(mg test item.L^-1)
typical	48	5.8

Based on the results of this study, the substance would not be classified as acute 1 to aquatic organisms in accordance with the classification of the CLP.

This toxicity study is considered as acceptable and can be used for that endpoint.