[No public or meaningful name is available]

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2019

Reliability:

2 (reliable with restrictions)

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:

1. SOFTWARE
Software Package: iSafeRat® HA-QSAR toolbox v2.4,
Contact KREATIS
Dr. Paul Thomas
KREATiS SAS
23, rue du Creuzat
38080 L’ISLE D’ABEAU
FRANCE

2. MODEL (incl. version number)
iSafeRat® HA-QSAR toolbox v2.4 – Daphnia Sp. (48-hour EC50); including the following specific sub-models:
(i) non-polar narcosis (MechoA 1.1)
01 February 2014 (model development); 30 November 2017 (current model version)

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See attached: ‘Prediction of acute toxicity of (2RS)-2-ethyl-4,4-dimethyl-1-cyclohexanone to Daphnia Sp. (48-hour EC50)’ version 1.0; dated 12 November 2019.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Full details of the method are provided in the attached QMRF named 'iSafeRat® HA-QSAR based on a holistic approach for predicting physicochemical and ecotoxicological endpoints’ version 1.8; 30 November 2017.

5. APPLICABILITY DOMAIN
See ‘any other information on results incl. tables’.
See attached See attached: ‘Prediction of acute toxicity of (2RS)-2-ethyl-4,4-dimethyl-1-cyclohexanone to Daphnia Sp. (48-hour EC50)’ version 1.0; dated 12 November 2019.

6. ADEQUACY OF THE RESULT
1) QSAR model is scientifically valid. 2) The substance falls within the applicability domain of the QSAR model. 3) The prediction is fit for regulatory purpose.
The prediction is adequate for the Classification and Labelling or risk assessment of the substance as indicated in REACH Regulation (EC) 1907/2006: Annex XI Section 1.3. Specifically when combined with further information such as physico-chemistry and environmental fate testing and modelling.

Guideline:

other: REACH Guidance on QSARs R.6, May/July 2008

Principles of method if other than guideline:

1. iSafeRat® HA-QSAR toolbox v2.4 – Daphnia Sp. 48h EC50 ; including the following specific sub-models:
(i) non-polar narcosis (MechoA 1.1)
2. Aquatic Toxicity Assessment using the Additivity Approach or based on a constituent and worst-case approach
3. Assessment of Degradability for the purpose of Classification and Labelling

Specific details on test material used for the study:

Detailed information on the 'test material identity' is provided in the attached QSAR Prediction Reporting Format (QPRF) document including information on individual constituents.

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

20 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: 95% Confidence Interval: 18 - 22 mg/L

1. Defined Endpoint:

QMRF 3. Ecotoxic effects

QMRF 3.1. Short-term toxicity to Daphnia (immobilisation)

Reference to type of model used and description of results:

iSafeRat® HA-QSAR toolbox v2.4 –Daphnia Sp. 48h EC50 ; including the following specific sub-models:

(i) non-polar narcosis (MechoA 1.1)

01 February 2014 (model development); 30 November 2017 (current model version)

 

2. Description of results and assessment of reliability of the prediction:

See attachment QPRF: ‘Prediction of acute toxicity of (2RS)-2-ethyl-4,4-dimethyl-1-cyclohexanone to Daphnia Sp. (48-hour EC50)’ version 1.0; dated 12 November 2019.

Results:

(2RS,4SR)-2-methyl-4-propyl-1,3-oxathiane: 48-h EC50 = 20 (C.I. 18 – 22) mg/L

 

Inputs Used for Test Item: All modelling was based on input of SMILES notation for each constituent of the test item and the process relied on modelled or measured values for Kow and water solubility to define each constituent prediction. This approach is in line with the attached QMRF named ‘iSafeRat® HA-QSAR based on a holistic approach for predicting physicochemical and ecotoxicological endpoints’ version 1.8; 30 November 2017, and ECHA Guidance on Information Requirements and Chemical Safety Assessment Chapter R7.b for hazard assessment of substances and complex mixtures.

 

For the purpose of concluding on classification and labelling for this substance either (i) the additivity formula from Annex I, Section 4.1.3.5.2 of CLP Regulation (EC) 1272/2008 is applied or (ii) a worst case application of 48-h EC50 effect levels is applied to known components of the substance. As applicable.

Substance rapidly degradable: No.

Log Kow: < 4.0 and BCF < 500 L/kg wet-wt (in silico models such as BCFBAF v3.01, US EPA and/or other models).

 

Assessment of the substance within the applicability domain as documented within the corresponding QMRF named ‘iSafeRat® HA-QSAR based on a holistic approach for predicting physicochemical and ecotoxicological endpoints’ version 1.8; 30 November 2017 – section 5; indicates the substance:

(i) Falls within the Log Kow and Water Solubilities domains: (log WSOL (mol/L) -4.63 to 0.87)

(ii) Falls within the structural fragment domain

(iii) Falls within the mechanistic domain of MechoA 1.1

  

3. Uncertainty of the prediction and mechanistic domain:

An external validation set is available for the chemical class used in this prediction however is not publicly available. Interested parties are invited to contact the model author. The QMRF has been peer reviewed by Joint Research Centre, ISPRA, Italy.

Full details on the training set, internal and external validations, as applicable are included in the attached QMRF named ‘iSafeRat® HA-QSAR based on a holistic approach for predicting physicochemical and ecotoxicological endpoints’ version 1.8; 30 November 2017. Interested parties are invited to contact the model author.

 

Uncertainty in the prediction relates to:

Statistical characteristics are provided (i) for the prediction: in the attached QPRF and (ii) for the model: in the attached QMRF, respectively.

Validity criteria fulfilled:

yes

Conclusions:

The results are adequate for the for the regulatory purpose.

Executive summary:

iSafeRat® HA-QSAR toolbox v2.4 – Daphnia Sp. 48h EC50 ; including the following specific sub-models:

(i) non-polar narcosis (MechoA 1.1)

Endpoint values: Daphnia Sp. 48-hr EC50: 20 (C.I. 18 - 22) mg/L

 

Adequacy of the QSAR:

1) QSAR model is scientifically valid. 2) The substance falls within the applicability domain of the QSAR model. 3) The prediction is fit for regulatory purpose.

The prediction is adequate for the Classification and Labelling or risk assessment of the substance as indicated in REACH Regulation (EC) 1907/2006: Annex XI Section 1.3. The predictions do not indicate extreme acute toxicities relevant for classification and labelling. The assessment indicates that the prediction is suitable for the regulatory conclusion in accordance with the tonnage driven information requirements.

Description of key information

QSAR: 48h-EC50 (invertebrates) = 20 (C.I. 18 - 22) mg/L, iSafeRat® HA-QSAR toolbox v2.4, KREATIS SAS, 2019

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

20 mg/L

Additional information

Key data : QSAR, iSafeRat® HA-QSAR toolbox v2.4, KREATIS SAS, 2019

iSafeRat® HA-QSAR toolbox v2.4 – Daphnia Sp. 48h EC50 ; including the following specific sub-models:

(i) non-polar narcosis (MechoA 1.1)

Endpoint values: Daphnia Sp. 48-hr EC50: 20 (C.I. 18 - 22) mg/L

 

Adequacy of the QSAR:

1) QSAR model is scientifically valid. 2) The substance falls within the applicability domain of the QSAR model. 3) The prediction is fit for regulatory purpose.

The prediction is adequate for the Classification and Labelling or risk assessment of the substance as indicated in REACH Regulation (EC) 1907/2006: Annex XI Section 1.3. The predictions do not indicate extreme acute toxicities relevant for classification and labelling. The assessment indicates that the prediction is suitable for the regulatory conclusion in accordance with the tonnage driven information requirements.

 

References for further information:

1. QMRF Title: ‘iSafeRat® HA-QSAR based on a holistic approach for predicting physicochemical and ecotoxicological endpoints’ version 1.8; 30 November 2017

2. QPRF Title: ‘Prediction of acute toxicity of (2RS)-2-ethyl-4,4-dimethyl-1-cyclohexanone to Daphnia Sp. (48-hour EC50)’ version 1.0; dated 12 November 2019