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

Toxicity to aquatic algae and cyanobacteria

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: estimation based on QSAR having unreliable QSAR regressions.

Justification for type of information:

QSAR prediction

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2008

Duration:

96 h

Dose descriptor:

EC50

Effect conc.:

2.22 mg/L

Remarks on result:

other: Acrylates

Duration:

96 h

Dose descriptor:

EC50

Effect conc.:

3.29 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:

no

Conclusions:

Depending on the ECOSAR class of the substance the EC50 is predicted to be between 2.22 and 3.29 mg/L. Only the regression for acrylates has a sufficiently high R2 (0.78) versus 0.3 for amides. Therefore, the 2.22 mg/L prediction was considered 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	21/08/2021
2.2	QPRF author and contact details	Karel Viaene [e-mail]
3.	Prediction
3.1	Endpoint (OECD Principle 1)	Endpoint	Ecotoxicity EC50 96h algae
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: 6.4 Amides: max MW: 1000 g/mol              Max Kow: 6.4   On-Line ECOSAR User’s Guide		Substance within range (948.05 g/mol and estimated Kow 3.593)
3.4	The uncertainty of the prediction (OECD principle 4)	Statistical accuracy for training dataset: Acrylates: N=10+1 r² = 0.78 Amides: N=18+6 r² = 0.30
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 algae, thus reflecting the chemical bioavailability.

 

 

 

Assessment of estimation domain:

 

Class	Applicability domain limits	Substance parameters
Acrylates	Max MW: 1000 g/mol Max Kow: 6.4	948.05 g/mol estimated Kow 3.593
Amides	Max MW: 1000 g/mol Max Kow: 6.4	948.05 g/mol estimated Kow 3.593

 

 

Reference 2

Endpoint:

toxicity to aquatic algae and cyanobacteria

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

Version / remarks:

2008

Dose descriptor:

EC50

Effect conc.:

9.93 mg/L

Remarks on result:

other: Based on the nearest neighbor method

Method	Predicted value -Log10(mol/L)
Hierarchical clustering	N/A
Group contribution	N/A
FDA	N/A
Nearest neighbor	4.98

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

Validity criteria fulfilled:

yes

Conclusions:

EC50, algae (growth inhibition study) is predicted to be 9.93 mg/L, based on the nearest neighbor algorithm of the T.E.S.T. program. A consensus score could not be calculated because only one of 4 algorithms predicted a value. Therefore, the prediction is uncertain.

Executive summary:

 

 

QPRF: TEST v4.2.1 (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: 0.72 FDA : R^2: 0.75 Group contribution: 0.68 Nearest neighbor : R^2: 0.60 Consensus: R^2: 0.76
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)

 

 

 

Reference 3

Endpoint:

toxicity to aquatic algae and cyanobacteria

Type of information:

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

Adequacy of study:

weight of evidence

Study period:

between 12 May 2006 and 31 July 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

Duration:

72 h

Dose descriptor:

EC10

Effect conc.:

1.4 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

biomass

Remarks on result:

other: 95% CL 0 - 3.6%

Duration:

72 h

Dose descriptor:

EC10

Effect conc.:

3.2 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

growth rate

Remarks on result:

other: 95%CL 1.8–4.6%

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

5 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

biomass

Remarks on result:

other: 95% CL 0.24–14

Duration:

72 h

Dose descriptor:

EC50

Effect conc.:

10 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

growth rate

Remarks on result:

other: 95%CL: 7.9–14%

Duration:

72 h

Dose descriptor:

EC90

Effect conc.:

18 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

biomass

Remarks on result:

other: 95% CL 7.8–60

Duration:

72 h

Dose descriptor:

EC90

Effect conc.:

33 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

growth rate

Remarks on result:

other: 95% CL 23–62

Duration:

72 h

Dose descriptor:

NOEC

Effect conc.:

0.78 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

biomass

Duration:

72 h

Dose descriptor:

NOEC

Effect conc.:

0.78 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

growth rate

Duration:

72 h

Dose descriptor:

LOEC

Effect conc.:

2.7 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

biomass

Duration:

72 h

Dose descriptor:

LOEC

Effect conc.:

2.7 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

growth rate

Details on results:

RESULTS AND DISCUSSION
At the start of the test, the measured test item concentrations in the analyzed test media ranged from 92 to 102% of the nominal values (see analytical results and Table 2 in the attached analytical phase report). This shows the correct preparation of the test media.

At the test concentrations of nominal 10 to 100 mg/L the test item was sufficiently stable during the test period of 72 hours (85 to 96% of the nominal test concentrations at test end). At nominal 1.0 to 3.2 mg/L, the test item concentrations decreased to 46 to 70% of nominal at the end of the 72 hour test period. The losses could be due to an adsorption of the test item onto the algae and/or glass surfaces.

The mean measured test concentrations (calculated as the geometric mean over all measurements per test concentration) varied in the range of 78 to 98% of the nominal values. Therefore, the reported biological results are based on the mean measured test item concentrations. The tabulated values represent rounded results obtained by calculation using the exact raw data.


Nominal test concentration (mg/L) Mean measured test item concentration (average over all measurements per test concentration) (mg/L)
0.32 not analyzed
1.0 0.78 (78% of nominal)
3.2 2.7 (83% of nominal)
10 8.8 (88% of nominal)
32 31 (96% of nominal)
100 98 (98% of nominal)

The influence of the test item 2-(2-Vinyloxyethoxy) ethyl acrylate on the growth of Scenedesmus subspicatus is shown in Tables 1–5 and Figure 1. The test item had a statistically significant inhibitory effect on the growth (biomass and growth rate) of Scenedesmus subspicatus after the test period of 72 hours at concentrations of 2.7 mg/L (nominal 3.2 mg/L) and above (results of Dunnett-tests, one-sided, α = 0.05, Tables 4 and 5). Thus, the test concentration of 2.7 mg/L was determined as the 72-hour LOEC (lowest concentration tested with toxic effects).

The 72-hour NOEC (highest concentration tested without toxic effects after a test period of 72 hours) was determined to be 0.78 mg/L, since up to and including this test concentration both the mean biomass and the mean growth rate of the algae were not statistically significantly lower than in the control (Tables 4 and 5).

The EC values as well as the NOEC and LOEC were calculated for both parameters, the algal biomass (b) and the growth rate (r), after 72 hours test duration, based on mean measured concentrations:
Parameter (0-72 h) Biomass b (mg/L) Growth rate r (mg/L)
EC50 5.0 10
95%-confidence limits 0.24–14 7.9–14
EC10 1.4 3.2
95%-confidence limits 0–3.6 1.8–4.6
EC90 18 33
95%-confidence limits 7.8–60 23–62
NOEC 0.78 0.78
LOEC 2.7 2.7

The microscopic examination of the algal cells after 72 hours exposure showed no difference between the algae growing in test medium with reduced algal growth (nominal 10 mg/L) and the algal cells in the control. There were no obvious effects on the shape and size of the algal cells growing in test media containing the test item at up to and including this nominal concentration.

At the start of the test, the pH values in the test media and the control ranged from 7.9 to 8.1 (Table 7). The pH increased during the test period and was in the range of 8.4 to 10.6 at test end, when measured in the volumes incubated for the analytical samples. The increase of the pH during the testwas obviously caused by the CO2-consumption of the algae due to their rapid growth or their high densities (although the test media have been intensively stirred). The pH measured in the actual test itself was in the range if 8.4 to 8.9 at test end. The differences in pH between the flasks with the analytical samples and the actual test are obviously caused by differences in the incubation flasks and the test medium volume (for analytical purpose volumes up to 100 mL per sample were needed).

Results with reference substance (positive control):

In the control the cell density increased from a nominal N = 1 × 104 cells/mL at the start of the test (0 hours) to N = 64 × 104 cells/mL (mean value) after 72 hours (Table 1). Thus, the algal growth in the control was sufficiently high under the conditions of the test. The validity criterion of increase of cell density by at least a factor of 16 over 72 hours was fulfilled. No remarkable observations were made concerning the appearance of the test media. All test media were clear solutions throughout the test period (Table 6).

Reported statistics and error estimates:

Calculation of LC10, LC50, LC90, NOEC and LOEC.

Dunnett's test.

For tables (1 -8) please see attachment 2.

Validity criteria fulfilled:

yes

Conclusions:

Parameter (0 – 72 hours) Biomass b (mg/L) Growth rate r (mg/L)
EC 50 – 95% confidence limits 5.0 (0.24 – 14) 10 (7.9 – 14)
EC 10 – 95% confidence limits 1.4 (0 – 3.6) 3.2 (1.8 – 4.6)
EC 90 – 95% confidence limits 18 (7.8 – 60) 33 (23 – 62)
NOEC 0.78 0.78
LOEC 2.7 2.7

Executive summary:

The influence of the test item 2 -2(Vinyloxyethoxyether ethyl acrylate on the growth of the green algal species Scenedesmus subspicatus was investigated in a 72 hour static test according to the EU commission Directive 92/69/EEC C.3, 1992 and the OECD Guideline No. 201, 1984.

The nominal test concentrations were 0.32,1.0, 3.2, 10, 32 and 100 mg/L in parallel with a control.

At the start of the test, the measured test item concentrations in the analyzed test media ranged from 92 to 102% of the nominal values. At the test concentrations of nominal 10 to 100 mg/L the test item was sufficiently stable during the test period of 72 hours (85 to 96% of the nominal test concentrations at test end). At nominal 1.0 to 3.2 mg/L, the test item concentrations decreased to 46 to 70% of nominal at the end of the 72 hour test period. The losses could be due to an adsorption of the test item onto the algae and/or glass surfaces.

The mean measured test concentrations (calculated as the geometric mean over all measurements per test concentration) varied in the range 78% to 98% of the nominal values. Therefore, the reported biological results are based on the mean measured test item concentrations.

Nominal test concentration (mg/L)	Mean measured test item concentration (average over all measurements per test concentration) (mg/L)
0.32	Not analysed
1	0.78
3.2	2.7
10	8.8
32	31
100	98

The test item had a statistically significant inhibitary effect on the growth (biomass and growth rate) of Scenedesmus subspicatus after the test period of 72 hours at concentrations of 2.7 mg/L and above (results of Dunnett-tests, one sided α = 0.05). Thus, the test concentration of 2.7 mg/L was determined as as the 72 -hour LOEC (lowest concentration tested with toxic effects after a test period of 72 hours) was determined to be 0.78 mg/L, since up to and including this test concentration both the mean and the biomass and the mean growth rate of the algae were not statistically significantly lower than in the control.

The EC values as well as the NOEC and LOEC were calculated for both parameters, the algal biomass (b) and the growth rate (r), after 72 hours test duration, based on mean measured test concentrations:

Parameter (0 – 72 hours)	Biomass b (mg/L)	Growth rate r (mg/L)
EC 50 – 95% confidence limits	5.0 (0.24 – 14)	10 (7.9 – 14)
EC 10 – 95% confidence limits	1.4 (0 – 3.6)	3.2 (1.8 – 4.6)
EC 90 – 95% confidence limits	18 (7.8 – 60)	33 (23 – 62)
NOEC	0.78	0.78
LOEC	2.7	2.7

Description of key information

The ECOSAR prediction (2.22 mg/l) was more reliable than the T.E.S.T. prediction. Read-across is moreover done to the 'arm' of the substance: VEEA (EC50: 10 mg/L).

Key value for chemical safety assessment

EC50 for freshwater algae:

2.22 mg/L