cis-2-methyl-4-propyl-1,3-oxathiane

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study performed under GLP. All relevant validity criteria were met.

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method C.2 (Acute Toxicity for Daphnia)

Deviations:

no

Qualifier:

according to guideline

Guideline:

ISO 6341 (Water quality - Determination of the Inhibition of the Mobility of Daphnia magna Straus (Cladocera, Crustacea))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

inspected: July 2016; signature: January 2017

Analytical monitoring:

yes

Details on sampling:

- Concentrations: Definitive test: analytically confirmed nominal concentrations: 0 (control), 32, 54, 92, 156 and 258 mg/L
Spacing factor (1.7) determined from range-finding test and physico-chemical properties of the substance.
Controls: test water without test substance but treated in the same way as the test substance solutions.
The target highest concentration was 265 mg/L. However, the highest nominal concentration could not be tested since the concentration of the stock solution of the test item was around 258 mg/L (mean of 3 replicates), which was therefore the highest tested concentration. This minor deviation from the study plan did not affect the integrity of the study given the biological results.
- Sampling method: Single samples for analysis were taken from the control and all test concentrations at the start and at the end of the test (t=48h)
- Sample storage conditions before analysis: Samples were used on day of sampling.

Vehicle:

no

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Common name: Daphinds
- Strain/clone: Daphnia magna (Straus), clone 5
- Justification for species other than prescribed by test guideline: Not applicable.
- Source: in-house laboratory cultures ; origin: LIEBE - CNRS UMR 7146 - UFR SciFA - Université de Lorraine Campus Bridoux
- Age of parental stock (mean and range, SD): < 24 hours.
- Method of breeding: Parthenogenesis
- Feeding during test: No.
- Food type: Not applicable
- Amount: Not applicable.
- Frequency: Not applicable.

ACCLIMATION
- Acclimation period: None.

Test type:

static

Water media type:

freshwater

Limit test:

yes

Total exposure duration:

48 h

Hardness:

Elendt M4 medium hardness: 250 mg/L expressed as CaCO3 and the pH: 6 to 9

Test temperature:

The temperature continuously measured in a temperature control vessel varied between 20.7 and 20.9°C during the test, and complied with the requirements as laid down in the protocol (18-22°C, constant within 1°C).

pH:

Test conditions remained within the limits prescribed by the guideline; pH: 7.40-8.08, not varying by more than 1.5 unit at the end of the test.

Dissolved oxygen:

Test conditions remained within the limits prescribed by the guideline; oxygen: > 3 mg/L at the end of the test.

Nominal and measured concentrations:

Range-finding test: analytically confirmed nominal concentrations: 0 (control), 1.0, 10.0, 32.0 and 100.0 mg/L
Definitive test: analytically confirmed nominal concentrations: 0 (control), 32, 54, 92, 156 and 258 mg/L
All concentrations after 48 hours were maintained within ± 20% analytically confirmed initial and nominal concentrations.

Details on test conditions:

TEST SYSTEM
- Test vessel: 60 mL
- Type (delete if not applicable): closed without headspace; static
- Material, size, headspace, fill volume: Glass, no headspace.
- Aeration: No aeration of the test solutions.
- Type of flow-through (e.g. peristaltic or proportional diluter): Not applicable.
- Renewal rate of test solution (frequency/flow rate): Not applicable.
- No. of organisms per vessel: Control and test item: 20 per concentration, 5 per vessel containing 60 mL of test solution
- No. of vessels per concentration (replicates): 4 (four replicates, 5 daphnia per vessel).
- No. of vessels per control (replicates): 4 (four replicates, 5 daphnia per vessel).
- No. of vessels per vehicle control (replicates): Not applicable.

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: Not reported. Reconstituted water (Elendt M4 medium), as prescribed by OECD Guideline 202.
- Culture medium different from test medium: No.

OTHER TEST CONDITIONS
- Adjustment of pH: None.
- Photoperiod: 16 hours light; 8 hours dark photoperiod daily
- Light intensity: Not reported.

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :
Immobility (including mortality): 24 hours and at 48 hours.

VEHICLE CONTROL PERFORMED: Not applicable.

RANGE-FINDING STUDY
- Test concentrations: analytically confirmed nominal concentrations: 0 (control), 1.0, 10.0, 32.0 and 100.0 mg/L
- Results used to determine the conditions for the definitive study: Yes.

Reference substance (positive control):

yes

Remarks:

potassium dichromate

Duration:

24 h

Dose descriptor:

EC50

Effect conc.:

109.941 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: 95% CL: 93.355 - 129.474 mg/L

Remarks:

based on analytically confirmed nominal concentrations

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

72.378 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: 95% CL: 68.731 -76.219 mg/L

Remarks:

based on analytically confirmed nominal concentrations

Details on results:

- Behavioural abnormalities: None
- Observations on body length and weight: Not applicable.
- Other biological observations: Not applicable.
- Mortality of control: No mortalities.
- Other adverse effects control: None.
- Abnormal responses: None.
- Any observations (e.g. precipitation) that might cause a difference between measured and nominal values: None. All concentrations after 48 hours were maintained within ± 20% analytically confirmed initial and nominal concentrations.
- Effect concentrations exceeding solubility of substance in test medium: No.

Results with reference substance (positive control):

- Results with reference substance valid?: Yes.
- Mortality: None. Acute immobilisation observed only.
- EC50/LC50: 24h-EC50 was 1.31 mg/L (expected 24h-EC50 0.6 to 2.1 mg/L).
- Other: The sensitivity of this batch of test organism was in agreement with the historical data based on the most recent sensitivity test using potassium dichromate reference substance.

Reported statistics and error estimates:

Statistical analyses were performed by the computer program ToxRat® Professional, version 3.2.1. Since the probit model was not appropriate, the trimmed Spearman-Karber method was used for estimation of the EC50 including the 95% confidence interval.

Table 1. pH and oxygen (mg/L) concentrations during the definitive test

	pH values		Dissolved oxygen concentration (mg/L)
Nominal Concentration (mg/L)	Initial 0 hours	End 48 hours	Initial 0 hours	End 48 hours
0 (Control)	8.07	7.40	8.65	8.35
32	8.06	7.86	8.65	8.39
54	8.07	7.91	8.64	8.58
92	8.08	7.90	8.62	8.54
156	8.07	7.94	8.65	8.50
258	8.08	7.92	8.61	8.41

 

Table 2. Number of introduced daphnids and incidence of immobility in the definitive test

Nominal concentration (mg test item/L)	Replicate	Number of daphnids exposed	Response at 24h		Response at 48h
			Number	Total %	Number	Total %
Control	1 2 3 4	5 5 5 5	0 0 0 0	0	0 0 0 0	0
32	1 2 3 4	5 5 5 5	0 0 0 0	0	0 0 0 0	0
54	1 2 3 4	5 5 5 5	0 0 0 0	0	0 0 0 0	0
92	1 2 3 4	5 5 5 5	5 3 5 2	75	5 5 5 4	95
156	1 2 3 4	5 5 5 5	2 2 2 2	40	5 5 5 5	100
258	1 2 3 4	5 5 5 5	5 5 5 5	100	5 5 5 5	100

Validity criteria fulfilled:

yes

Conclusions:

The test item 48h-EC50 was 72.378 mg/L (95% CL: 68.731 – 76.219 mg/L) based on analytically confirmed nominal concentrations.

Executive summary:

The acute toxicity to Daphnia magna was examined according to OECD TG 202 Daphnia Sp., Acute Immobilisation Test and EU Method C.2 guidelines under GLP. Following a preliminary range-finding test, twenty daphnids (four replicates, five daphnids per replicate) were exposed to an aqueous solution of the test item over 48 hours at the required nominal test concentrations 32, 54, 92, 156 and 258.0 mg/L and to a control. The immobilisation of the daphnids was determined in a closed static 48-hour test by visual observation after 24 and 48 hours. Samples taken from the control and all test concentrations and analysis indicated that the concentrations at 48 hours were to be within ± 20% of the initial and nominal concentrations. Therefore indicated as to be satisfactorily maintained throughout the test and therefore the evaluation of effects was based on analytically confirmed nominal concentrations. The trimmed non-parametric test (Spearman-Karber method) was used for estimation of the EC50 including the 95% confidence interval as the probit model was determined not appropriate. The study met the relevant study acceptability criteria and was considered valid. The 24-h EC50 was 109.941 (C.I. 93.355 – 129.474) mg/L and the 48-h EC50 was 72.378 (C.I. 68.731 – 76.219) mg/L based on analytically confirmed nominal concentrations.

Reference 2

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2014

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
Estimation Programme Interface (EPI) Suite programme for Microsoft Windows v4.11
Contact EPISuite:
U.S. Environmental Protection Agency
1200 Pennsylvania Ave.
N.W. (Mail Code 7406M)
Washington, DC 20460

2. MODEL (incl. version number)
ECOSAR v1.11 – Daphnid 48h LC50
19 June 2012 (model development)

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See attached: ‘QPRF Title: Substance: EC 261-699-8 using the model ECOSAR v1.11 for the endpoint: Daphnid 48h LC50’ version 1.0; dated 30 September 2014.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Full details of the method are provided in the attached QMRF named ‘QMRF Title: ECOSAR v1.11 Daphnid 48h LC50’ version 1.0; dated 14 August 2014.

5. APPLICABILITY DOMAIN
See ‘any other information on results incl. tables’.
See attached: ‘QPRF Title: Substance: EC 261-699-8 using the model ECOSAR v1.11 for the endpoint: Daphnid 48h LC50’ version 1.0; dated 30 September 2014.

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

Guideline:

EPA OPPTS 850.1010 (Aquatic Invertebrate Acute Toxicity Test, Freshwater Daphnids)

Version / remarks:

This guideline is preferred for the training set but not obligatory

Principles of method if other than guideline:

ECOSAR v1.11 - Daphnid 48h LC50 ; Neutral Organics Class

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

10.785 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

mobility

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:

ECOSAR v1.11 - Daphnid 48h LC50 ; Neutral Organics Class, 24 July 2012

 

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

Ecosar Class:

Neutral Organic SAR (baseline toxicity): Daphnid 48-hr LC50: 10.785 mg/L

Assessment of the substance within the applicability domain as documented within the corresponding QMRF named ‘QMRF Title: ECOSAR v1.11 Daphnid 48h LC50’ version 1.0; 13 August 2014 – section 5; indicates the substance:

(i) Falls within the Log Kow domain of < 5 (general domain for the model; and Neutral Organics class specific cut off); (ii) Molecular weight is < 1000 g/mol and; (iii) Effect levels are predicted below the water solubility.

The substance does not possess functional groups outside those included within the esters, neutral organics or mono-epoxides classes and training sets. The assigned chemical class Neutral Organic is appropriate to the substance. The ECOSAR QSAR model as detailed is not known to function by specific modes of action; although the target is not expected to have toxicity exceeding baseline non-polar narcosis encorporated within the chemical class assigned. Full references to training set data are presented within ECOSAR v1.1 Help System; if not proprietary (in such cases the chemical identification is listed as CBI, but the relevant descriptor data are provided). A summary of this information is presented by the applicant.

The substances in the training set are considered analogues to the target substance since they possess a functions covered within the Neutral Organics class; Log Kow < 5 and MW < 1000 g/mol. The substance and the structural analogues share a common functional groups and physic-chemical domains. The ECOSAR class is based on similar relationships between toxicity and the various types of pharmacologic properties.

 

3. Uncertainty of the prediction and mechanistic domain:

The coefficients of determination for the chemical class training set is published as presented below:

Neutral Organics: Coefficient of determination (r2) = 0.7704

Data for the Neutral Organics Class training set are available via external validation (see attached QMRF prepared by the applicant for full citations of the relevant validations). Consistency of ECOSAR data compared to measured toxicity showed 64-67 % of Daphnia predictions (all chemical classes assessed) were within a tolerance factor of 10, comparable to that seen in Hulzebos & Posthumus (2003). Uncertainty in the prediction relates to the limited external validation on the relevant classes and the limited applicability of the model in relation to isomers. Model predictivity could be improved by the assignment of additional chemical categories and expansion of sub-structure rules, in addition further substances addition to the training set and rules for stereochemical effects within the model would improve predictivity.

 

The ECOSAR QSAR model as detailed is not known to function by specific modes of action associated with the chemical class(es) assigned. ECOSAR classes are grouped based on similar relationships between toxicity and the various types of pharmacologic properties. The model does not apply a mechanistic approach to assessment of toxicity other than assignment of chemical classes (to identify potential toxicity in excess of baseline narcosis) using an expert decision tree. The selected classes appear appropriate to the substance based on expert assessment.

Validity criteria fulfilled:

yes

Conclusions:

The results are adequate for the regulatory purpose.

Executive summary:

ECOSAR v1.11 - Daphnid 48h LC50 ; Neutral Organics Class, 24 July 2012

Ecosar Class:

Neutral Organic SAR (baseline toxicity): Daphnid 48h LC50: 10.785 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.

Reference 3

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2018

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,4SR)-2-methyl-4-propyl-1,3-oxathiane to Daphnia Sp. (48-hour EC50)’ version 1.0; dated 09 April 2018.

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,4SR)-2-methyl-4-propyl-1,3-oxathiane to Daphnia Sp. (48-hour EC50)’ version 1.0; dated 09 April 2018.

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.:

40 mg/L

Nominal / measured:

meas. (not specified)

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: 95% Confidence Interval: 36 - 44 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,4SR)-2-methyl-4-propyl-1,3-oxathiane to Daphnia Sp. (48-hour EC50)’ version 1.0; dated 09 April 2018.

Results:

(2RS,4SR)-2-methyl-4-propyl-1,3-oxathiane: 48-h EC50 = 40 (C.I. 36 – 44) 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: 40 (C.I. 36 - 44) 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

48h-EC50 (invertebrates) = 72.378 (C.I: 68.731 – 76.219) mg/L based on analytically confirmed nominal concentrations, 48-hour, freshwater, OECD TG 202, 2018

Supporting information:

QSAR: 48h-EC50 (invertebrates) = 40 (C.I. 36 - 44) mg/L, iSafeRat® HA-QSAR toolbox v2.4, KREATIS SAS, 2018

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

72.378 mg/L

Additional information

Key data: OECD TG 202, 2018 : The acute toxicity to Daphnia magna was examined according to OECD TG 202 Daphnia Sp., Acute Immobilisation Test and EU Method C.2 guidelines under GLP. Following a preliminary range-finding test, twenty daphnids (four replicates, five daphnids per replicate) were exposed to an aqueous solution of the test item over 48 hours at the required nominal test concentrations 32, 54, 92, 156 and 258.0 mg/L and to a control. The immobilisation of the daphnids was determined in a closed static 48-hour test by visual observation after 24 and 48 hours. Samples taken from the control and all test concentrations and analysis indicated that the concentrations at 48 hours were to be within ± 20% of the initial and nominal concentrations. Therefore indicated as to be satisfactorily maintained throughout the test and therefore the evaluation of effects was based on analytically confirmed nominal concentrations. The trimmed non-parametric test (Spearman-Karber method) was used for estimation of the EC50 including the 95% confidence interval as the probit model was determined not appropriate. The study met the relevant study acceptability criteria and was considered valid. The 24-h EC50 was 109.941 (C.I. 93.355 – 129.474) mg/L and the 48-h EC50 was 72.378 (C.I. 68.731 – 76.219) mg/L based on analytically confirmed nominal concentrations.

 

Supporting data:

1. QSAR, iSafeRat® HA-QSAR toolbox v2.4, KREATIS SAS, 2018

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: 40 (C.I. 36 - 44) 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.

 

2. QSAR, ECOSAR v1.11, US EPA, 2014

ECOSAR v1.11 - Daphnid 48h LC50 ; Neutral Organics Class

Ecosar Class: Neutral Organic SAR (baseline toxicity):

Daphnid 48h LC50: 10.785 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.

 

Weight of evidence conclusion:

An available OECD TG 202 (2018) Daphnia Sp. study indicates a 48-h EC50 of 72.378 (C.I: 68.731 – 76.219) mg/L which is selected as the key study and the basis of the effect levels for classification and labelling. The iSafeRat® HA-QSAR toolbox v2.4 prediction model indicates an EC50 of 40 (C.I. 36 - 44) mg/L. It can be seen that the iSafeRat® model provides highly conservative predictions when compared with the experimentally measured effect levels of freshwater aquatic invertebrates for the chemical class. The ECOSAR v1.11 model predictions on the substance are discarded due to demonstratable over prediction of toxicity and lower model performance, when compared with the iSafeRat® HA-QSAR toolbox v2.4 prediction model versus measured data.

 

References for further information:

1. Applicant study, OECD TG 202, 2018

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

3. QPRF Title: ‘Prediction of acute toxicity of (2RS,4SR)-2-methyl-4-propyl-1,3-oxathiane to Daphnia Sp. (48-hour EC50)’ version 1.0; dated 09 April 2018

4. QMRF Title: ‘ECOSAR v1.11 Daphnid 48h LC50’ version 1.0; dated 14 August 2014

5. QPRF Title: ‘Substance: EC 261-699-8 using the model ECOSAR v1.11 for the endpoint: Daphnid 48h LC50’ version 1.0; dated 30 September 2014