2-Propenoic acid, 1,1'-[7,13-dimethyl-10-(3-methyl-11-oxo-2,4,7,10-tetraoxatridec-12-en-1-yl)-10-[[2-[(9-oxo-9H-thioxanthen-2-yl)oxy]acetyl]amino]-3,6,8,12,14,17-hexaoxanonadecane-1,19-diyl] ester

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:

(Q)SAR

Adequacy of study:

weight of evidence

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
ECOSAR v2.0

2. MODEL (incl. version number)
ECOSAR v2.0

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CC(OCCOCCOC(=O)C=C)OCC(COC(C)OCCOCCOC(=O)C=C)(COC(C)OCCOCCOC(=O)C=C)NC(=O)COC1C=CC2=C(C=1)C(=O)C1C=CC=CC=1S2

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
[[Explain how the model fulfils the OECD principles for (Q)SAR model validation. Consider attaching the QMRF and/or QPRF or providing a link]
See attached documents

5. APPLICABILITY DOMAIN
[Explain how the substance falls within the applicability domain of the model]
See attached documents.
Substance was considered as an acrylate and an amide.

6. ADEQUACY OF THE RESULT
[Explain how the prediction fits the purpose of classification and labelling and/or risk assessment]
Predictions are useful in a weight of evidence approach.

Qualifier:

according to guideline

Guideline:

other: Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals

GLP compliance:

not specified

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

11.24 mg/L

Remarks on result:

other: Acrylates

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

11.57 mg/L

Remarks on result:

other: Amides

Chemicals may not be soluble enough to measure this predicted effect. If the effect level excees the water solubility by 10x, typically no effects at saturation (NES) are reported.

Validity criteria fulfilled:

yes

Conclusions:

Depending on the ECOSAR class of the substance the EC50 is predicted to be between 11.24 and 11.54 mg/L. The R2 for the amide regression was markedly higher (0.6 vs 0.27) and therefore the 11.57 mg/L was considered the most reliable.

Executive summary:

 

QPRF: ECOSAR v1.11 (11 09 2014)

 

1.	Substance	See “Test material identity”
2.	General information
2.1	Date of QPRF	05/08/2021
2.2	QPRF author and contact details	Karel Viaene [e-mail]
3.	Prediction
3.1	Endpoint (OECD Principle 1)	Endpoint	Ecotoxicity LC50 48h daphnid
3.2	Algorithm (OECD Principle 2)	Model or submodel name	ECOSAR
		Model version	v. 2.0
		Predicted value (model result)	See “Results and discussion”
		Input for prediction	Chemical structure via SMILES
		Descriptor values	Class specific Estimations
3.3	Applicability domain (OECD principle 3)	Domains:
		Acrylates: max MW: 1000 g/mol              Max Kow: 5.0 Amides: max MW: 1000 g/mol              Max Kow: 5   On-Line ECOSAR User’s Guide		Substance within range (948.05 g/mol and estimated Kow 3.593) LC50 does not exceed the water solubility by 10x: Water solubility is determined at 4.87 mg/L. This parameter is therefore fulfilled.
3.4	The uncertainty of the prediction (OECD principle 4)	Statistical accuracy for training dataset: Acrylates: N=13+2 r² = 0.28 Amides: N=23+17 r² = 0.60
3.5	The chemical mechanisms according to the model underpinning the predicted result (OECD principle 5)	The model largely relies on logKow, which typically is the main descriptor: log P is linked to the partitioning of the substance from water into the lipid phase of the daphnids, thus reflecting the chemical bioavailability.

 

 

 

Assessment of estimation domain:

 

Class	Applicability domain limits	Substance parameters
Acrylates	Max MW: 1000 g/mol Max Kow: 5.0	948.05 g/mol estimated Kow 3.593
Amides	Max MW: 1000 g/mol Max Kow: 5.0	948.05 g/mol estimated Kow 3.593

 

The LC50 values do not exceed the water solubility by 10x.

Reference 2

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

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
T.E.S.T. v4.2.1

2. MODEL (incl. version number)
T.E.S.T. v4.2.1

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CC(OCCOCCOC(=O)C=C)OCC(COC(C)OCCOCCOC(=O)C=C)(COC(C)OCCOCCOC(=O)C=C)NC(=O)COC1C=CC2=C(C=1)C(=O)C1C=CC=CC=1S2

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
[[Explain how the model fulfils the OECD principles for (Q)SAR model validation. Consider attaching the QMRF and/or QPRF or providing a link]
See attached documentation

5. APPLICABILITY DOMAIN
[Explain how the substance falls within the applicability domain of the model]
See attached documentation

6. ADEQUACY OF THE RESULT
[Explain how the prediction fits the purpose of classification and labelling and/or risk assessment]
Useful as part of a weight of evidence approach.

Qualifier:

according to guideline

Guideline:

other: Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals

GLP compliance:

not specified

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

76.42 mg/L

Remarks on result:

other: Nearest Neighbour method

 

 

Method	Duration	EndPt	Predicted (mg/L)
Consensus method	48 hr	LC50	N/A
Hierarchical clustering method	48 hr	LC50	N/A
Single model method	48 hr	LC50	N/A
Group contribution	48 hr	LC50	N/A
Nearest neighbor method	48 hr	LC50	76.42
FDA	48 hr	LC50	N/A

 

The consensus prediction for this chemical is considered unreliable since only one prediction can only be made

 

       Hierarchical method:The toxicity for a given query compound is estimated using the weighted average of the predictions from several different models. The different models are obtained by using Ward’s method to divide the training set into a series of structurally similar clusters. A genetic algorithm based technique is used to generate models for each cluster. The models are generated prior to runtime.

       FDA method: The prediction for each test chemical is made using a new model that is fit to the chemicals that are most similar to the test compound. Each model is generated at runtime.

       Single model method: Predictions are made using a multilinear regression model that is fit to the training set (using molecular descriptors as independent variables) using a genetic algorithm based approach.        The regression model is generated prior to runtime.

       Nearest neighbor method: The predicted toxicity is estimated by taking an average of the 3 chemicals in the training set that are most similar to the test chemical.

          Consensus method: The predicted toxicity is estimated by taking an average of the predicted toxicities from the above QSAR methods (provided the predictions are within the respective applicability domains)

 

Validity criteria fulfilled:

yes

Conclusions:

TEST QSAR estimates the LC50 daphnia (48h) to be 76.42 mg/L, based on the nearest neighbour method. A consensus value could not be calculated as only one out of 5 methods resulted in a prediction.

Executive summary:

 

 

QPRF: TEST v4.01 (21 08 2021)

 

1.	Substance	See “Test material identity”
2.	General information
2.1	Date of QPRF	21/08/2021
2.2	QPRF author and contact details	Karel Viaene [e-mail]
3.	Prediction
3.1	Endpoint (OECD Principle 1)	Endpoint	Ecotoxicity LC50 48h daphnid
3.2	Algorithm (OECD Principle 2)	Model or submodel name	T.E.S.T.
		Model version	v. 4.2.1
		Predicted value (model result)	See “Results and discussion”
		Input for prediction	Chemical structure via SMILES
		Descriptor values	Class specific Estimations
3.3	Applicability domain (OECD principle 3)	Domains:
		-      Compounds can only contain the following element symbols: C, H, O, N, F, Cl, Br, I, S, P, Si or As -      Compounds must represent a single pure component		-Substance contains only allowed elements -Substance represents a single pure component
3.4	The uncertainty of the prediction (OECD principle 4)	Statistical external validation for 48 hour Daphnia magna LC50: Hierarchical: R^2: 0.695 Single Model: R^2: 0.697 FDA : R^2: 0.565 Group contribution: 0.671 Nearest neighbor : R^2: 0.733 Consensus: R^2: 0.739
3.5	The chemical mechanisms according to the model underpinning the predicted result (OECD principle 5)	Hierarchical method:The toxicity for a given query compound is estimated using the weighted average of the predictions from several different models. The different models are obtained by using Ward’s method to divide the training set into a series of structurally similar clusters. A genetic algorithm based technique is used to generate models for each cluster. The models are generated prior to runtime. FDA method: The prediction for each test chemical is made using a new model that is fit to the chemicals that are most similar to the test compound. Each model is generated at runtime. Nearest neighbor method: The predicted toxicity is estimated by taking an average of the 3 chemicals in the training set that are most similar to the test chemical. Group contribution: Fragment counts (such as the number of methyl and hydroxyl groups in a compound) are used to fit a multiple linear regression model to the entire data set. Consensus method: The predicted toxicity is estimated by taking an average of the predicted toxicities from the above QSAR methods (provided the predictions are within the respective applicability domains) Single model: Predictions are made using a multilinear regression model that is fit to the training set (using molecular descriptors as independent variables).

 

 

 

Reference 3

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

Between May 12th, 2006 and July 31st, 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
[Please provide information for all of the points below. Indicate if further information is included as attachment to the same record, or elsewhere in the dataset (insert links in 'Cross-reference' table)]

See attached justification

Reason / purpose for cross-reference:

read-across source

GLP compliance:

not specified

Duration:

24 h

Dose descriptor:

EC50

Effect conc.:

96 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

other: immobilisation

Duration:

24 h

Dose descriptor:

EC0

Effect conc.:

50 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

other: immobilisation

Duration:

24 h

Dose descriptor:

EC100

Effect conc.:

> 100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

other: immobilisation

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

55 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: 95% CL 40 - 77mg/L

Duration:

48 h

Dose descriptor:

EC0

Effect conc.:

25 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

48 h

Dose descriptor:

NOEC

Effect conc.:

25 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Duration:

48 h

Dose descriptor:

EC100

Effect conc.:

100 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Details on results:

- Behavioural abnormalities: None stated
- Observations on body length and weight: Not stated in report
- Other biological observations: None stated
- Mortality of control: None
- Other adverse effects control: None
- Abnormal responses: none stated
- Any observations (e.g. precipitation) that might cause a difference between measured and nominal values: none reported

The biological results are listed in Table 1.

During the first 24 hours of the test no immobility of the test organisms was observed in the control and up to and including the test item concentration of 50 mg/L. At the highest test concentration of 100 mg/L, 55% of the test organisms were found to be immobile.

The 24-hour EC50 of the test item was calculated to be 96 mg/L (95% confidence limits not calculable). The 24-hour EC0 was 50 mg/L, the 24-hour EC100 was > 100 mg/L.

After 48 hours of exposure no immobility of the test organisms was observed in the control and up to and including the test item concentration of 25 mg/L. At the concentration of 50 mg/L, 35% of the daphnids were found to be immobile. At the highest test concentration of 100 mg/L all test organisms were immobile after the exposure period of 48 hours. The 48-hour EC50 was calculated to be 55 mg/L with 95% confidence limits from 40 to 77 mg/L.

The 48-hour EC0 and the 48-hour NOEC (highest concentration tested without toxic effects after 48 hours) of 2-(2-Vinyloxyethoxy) ethyl acrylate were both 25 mg/L, since no immobilization was observed in the test organisms exposed to the test item at levels of up to and including this test concentration. The 48-hour EC100 was 100 mg/L.

No remarkable observations were made concerning the appearance of the test media. All test media were clear solutions throughout the entire test duration.

Results with reference substance (positive control):

- Results with reference substance valid?
Yes

- Mortality:
No mortalities recorded.

- EC50/LC50:
After 48 hours of exposure no immobility of the test organisms was observed in the control.

Reported statistics and error estimates:

None stated in report

Table 1:

Nominal test item concentration	No. of daphnids tested	Immobilized daphnids after 24 hours		Immobilized after 48 hours
		No.	%	No.	%
control	20	0	0	0	0
6.3	20	0	0	0	0
12.5	20	0	0	0	0
25	20	0	0	0	0
50	20	0	0	7	35
100	20	11	55	20	100

Validity criteria fulfilled:

yes

Conclusions:

After 48 hours of exposure no immobility of the test organisms was observed in the control and up to and including the test item concentration of 25 mg/L. At the concentration of 50 mg/L, 35% of the daphnids were found to be immobile. At the highest test concentration of 100 mg/L all test organisms were immobile after the exposure period of 48 hours. The test gave an EC50 value of 55mg/l and an NOEC value of 25 mg/l

Executive summary:

The acute toxicity of the test item 2-(2-Vinyloxyethoxy) ethyl acrylate to Daphnia magna was determined in a 48-hour static test according to the EU Commission Directive 92/69/EEC, Part C.2 (1992), and the OECD Guideline for Testing of Chemicals, No. 202 (2004). The nominal test item concentrations tested were 6.3, 12.5, 25, 50 and 100 mg/L. Additionally, a control was tested in parallel. The analytically determined concentrations of the test item in the analyzed test media from the sampling times at the start, after 24 hours and at the end of the test were between 93 and 101% of the nominal values. Thus, the test item 2-(2-Vinyloxyethoxy) ethyl acrylate was stable during the test period of 48 hours under the conditions of the test, and the reported biological results are based on the nominal concentrations of the test item.

The biological test results:

− 24-hour EC50: 96 mg/L (95% confidence limits not calculable)

− 24-hour EC0: 50 mg/L

− 24-hour EC100: > 100 mg/L

− 48-hour EC50: 55 mg/L (95% confidence limits: 40 - 77 mg/L)

− 48-hour EC0 and

48-hour NOEC: 25 mg/L

− 48-hour EC100: 100 mg/L

Description of key information

The ECOSAR and TEST predictions for this endpoint are reliable. Read-across is moreover done to the 'arm' of the substance: VEEA (EC50: 55 mg/L mobility). The lowest reliable endpoint is used for CSA: 11.57 mg/L.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Dose descriptor:

EC50

Effect concentration:

11.57 mg/L