Reaction products of 2-hydroxyethyl methacrylate and diphosphorous pentoxide and water

Adsorption / desorption

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

adsorption / desorption: screening

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2021

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)
KOCWIN v2.00
September 2010 (model development); November 2012 (model publication)

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See QPRF attached: ‘QPRF Title: Substance: Reaction products of 2-hydroxyethyl methacrylate and diphosphorous pentoxide and water using the model KOCWIN v2.00 for the endpoint: Soil Adsorption Coefficient (Koc)’ version 1.0 ; dated 04 March 2021.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Full details of the method are provided in the attached QMRF named ‘QMRF Title: KOCWIN v2.00: Soil Adsorption Coefficient (Koc)’ version 1.02; 04 March 2021.

5. APPLICABILITY DOMAIN
See ‘any other information on results incl. tables’.
See QPRF attached: ‘QPRF Title: Substance: Reaction products of 2-hydroxyethyl methacrylate and diphosphorous pentoxide and water using the model KOCWIN v2.00 for the endpoint: Soil Adsorption Coefficient (Koc)’ version 1.0 ; dated 04 March 2021.

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 contributing information to the environmental fate and transport and distribution assessment of the substance. The prediction is also supporting information for the Classification and Labelling or risk assessment of the substance as indicated in REACH Regulation

Reason / purpose for cross-reference:

other:

Reason / purpose for cross-reference:

reference to other study

Reason / purpose for cross-reference:

reference to other study

Guideline:

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

Principles of method if other than guideline:

Full details of the method are provided in the attached corresponding QMRF named ‘QMRF Title: KOCWIN v2.00: Soil Adsorption Coefficient (Koc)’ version 1.02; 04 March 2021.
- The model applies the following methodology to generate predictions:
(1) MCI model: first-order Molecular Connectivity Index with Fragment (group contribution) correction based QSAR; based on multiple linear-regression modelling
(2) Log Kow Regression mode: thermodynamic relationship model with Fragment (group contribution) correction based QSAR; based on multiple linear-regression modelling

- The model and the training and validation sets are published by US Environmental Protection Agency (USA).
The experimental Koc values in the training set and validation set were measured using one or more methods equivalent or similar to the following guidelines:
- HPLC method (OECD TG 121, 2001)
- Sediment and soil adsorption/desorption isotherm; screening method using three soil types (US EPA guideline OPPTS 835.1220, 1996)
- Batch equilibrium method (OECD TG 106, 2000)
- Leaching in Soil Columns method (Kd) (OECD TG 312, 2002)
- Simulation tests and direct field measurement (OECD Guidance Document 22, 2000)

Relevant EU (1992 as amended) may be also have been used where appropriate. It is understood that the core data of the training set would have been generated by non-HPLC method direct measurements of KOC. Additional data may have been subsequently added utilising estimates from the HPLC method in the model update from PCKOCWIN v1.0 to KOCWIN v2.0 and incorporation of Schuurmann et al. (2006) and other data.
- Justification of QSAR prediction: blocks under the ‘block method’ of environmental risk assessment. This is given the constituents comparable chemistries and physico-chemical properties. The substance consists of blocks of constituents of predicted Log Kow < 4.0. This was subsequently confirmed by experimental measurement (OECD TG 117, 2021) which demonstrated a Log Kow < 3.0. Consequently, the substance is not expected to have significant adsorption potential in the environmentally relevant pH range (pH 4 to pH 9). The model predictions are supporting of the waiving of testing for adsorption on the following basis :
In accordance with REACH Regulation (EC) No. 1907/2006 Annex VIII, column 2 section 9.3.1 the study does not need to be conducted if based on the physicochemical properties the substance can be expected to have a low potential for adsorption (e.g. the substance has a low octanol water partition coefficient). The substance possesses a measured Log Kow < 3.0 for all identified constituents and does not possess additional confounding properties (e.g. relevant ionisation potential) which affects partitioning behaviour within the environmentally relevant pH range (pH 4, 7 and 9). At these pH the substance constituents should exhibit maximum water solubility in addition. The applicant adapts the information requirement in accordance with the relevant testing strategy by providing measured and predicted QSAR log Pow for n-octanol/water partition coefficient and supporting QSAR predictions for log Koc in accordance with REACH Regulation (EC) 1907/2006: Annex XI Section 1.3, which demonstrates low potential for significant adsorption. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7a: Endpoint Specific Guidance, R.7.1.15, July 2017) the study does not need to be conducted.

Media:

soil

Type:

log Koc

Value:

>= -0.4 - <= 2.114 dimensionless

pH:

7

Temp.:

25 °C

Matrix:

Soil

Remarks on result:

other: Value represents the range of predicted Log Koc for all constituents

Remarks:

All predictions are based on the KOCWIN v2.00: Log Kow Regression sub-model due to greater domain applicability

Type:

Koc

Value:

>= 0.398 - <= 130.1 L/kg

pH:

7

Temp.:

25 °C

Matrix:

Soil

Remarks on result:

other: Value represents the range of predicted Log Koc for all constituents

Remarks:

All predictions are based on the KOCWIN v2.00: Log Kow Regression sub-model due to greater domain applicability

Transformation products:

no

1. Defined Endpoint:

QMRF 2. Environmental Fate Parameters

QMRF 2.7. Adsorption/Desorption in soil

Reference to type of model used and description of results:

KOCWIN v2.00; integrated within the Estimation Programme Interface (EPI) Suite programme for Microsoft Windows v4.11; September 2010 (model development); November 2012 (model publication)

 

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

The predicted values are provided within the QPRF attached: ‘QPRF Title: Substance: Reaction products of 2-hydroxyethyl methacrylate and diphosphorouspentoxide and water using the model KOCWIN v2.00 for the endpoint: Soil Adsorption Coefficient (Koc)’ version 1.0 ; dated 04 March 2021.

KOCWIN v2.00 (model publication: November 2012)

All predictions are based on the KOCWIN v2.00: Log Kow Regression sub-model due to greater domain applicability than the MCI Regression sub-model. Further details are provided below.

 Koc range (all constituents): >= 0.3978 to <= 130.1 L/Kg

Log Koc range (all constituents): >= -0.4004 to <= 2.114

The range of constituents was: Log Koc = -0.4004 to 2.114 in three blocks, respectively.

The majority of constituents had Log Koc = ca. 1.0 to 1.4

The substance consists of blocks of constituents of predicted Log Kow < 4.0. This was subsequently confirmed by experimental measurement (OECD TG 117, 2021) which demonstrated a Log Kow < 3.0. Consequently, the substance is not expected to have significant adsorption potential in the environmentally relevant pH range (pH 4 to pH 9)

 

Table 1.0 – Range of constituents

Constituent Number	Constituent Name (IUPAC)	Molecular Weight	Log Kow (KOWWIN)	Log Koc
1	phosphoric acid	97.9952	-0.7699	MCI model: 0.1484 Log Kow model: 0.6025
2	2-(dimethylphosphoryl)ethyl 2-methylbutanoate	206.222	0.6535	MCI model: 1.000 Log Kow model: 1.3224
3	2-hydroxyethyl methacrylate	130.1418	0.3014 Experimental: 0.47 Hansch, (1995)	MCI model: 0.1643 Log Kow model: 0.7080
4	2-hydroxyethyl 2-hydroxy-2-methylpropanoate	148.158	-0.7879	MCI model: 0.0000 Log Kow model: -0.4004
5	{2-[(2-methylprop-2-enoyl)oxy]ethoxy}phosphonic acid	210.1217	0.2199	MCI model: 1.0000 Log Kow model: 1.0845
6	bis({1-[(2-methylprop-2-enoyl)oxy]ethoxy})phosphinic acid	322.2482	1.0627	MCI model: 1.4341 Log Kow model: 1.4836
7	2-{[bis({2-[(2-methylprop-2-enoyl)oxy]ethoxy})phosphoryl]oxy}ethyl 2-methylprop-2-enoate	434.378	2.1995	MCI model: 3.5399 Log Kow model: 2.1141
8	{[hydroxy({2-[(2-methylprop-2-enoyl)oxy]ethoxy})phosphoryl]oxy}phosphonic acid	290.101	-0.7490	MCI model: 1.7365 Log Kow model: 0.5480
9	{[hydroxy({[hydroxy({2-[(2-methylprop-2-enoyl)oxy]ethoxy})phosphoryl]oxy})phosphoryl]oxy}phosphonic acid	370.079	-1.7179	MCI model: 2.6264 Log Kow model: 0.0115

All predictions are based on the KOCWIN v2.00: Log Kow Regression sub-model due to greater domain applicability than the MCI Regression sub-model. Further details are provided below.

  

It is noted by the applicant that the option of the KOCWIN v2.00 output of sub-models applicability: MCI regression and/or Log Kow regression is based on expert judgement. There are no transformations of units. The model programme is able to transform the units (Koc) to the coefficient of the logarithm scale (Log Koc). The result is then compared with the ranges of adsorption that are utilised in environmental fate modelling using expert systems. Additional criteria may apply if appropriate when interpreting the result for relevant endpoints. There is no universally acknowledged applicability domain for the model. However, assessment of the substance within the applicability domains recommended by the developers is documented within the corresponding QMRF named ‘QMRF Title: KOCWIN v2.00: Soil Adsorption Coefficient (Koc)’ version 1.02; 04 March 2021 – section 5; indicates the substance (constituents):

(i) All constituents fall within the Molecular Weight range domain.

(ii) No constituent substances have functional groups or features not in the training set of the model and/or for which no fragment constants and correction factors are available. Constituents 8 and 9 contain multiple P=O fragment instances, greater than the maximum of the training set although and/or those instances are specified within the programme as limited to two instances contribution limit to the MCI model calculation (i.e. “Counted only once per structure, regardless of number of occurrences”) (see QMRF title section 9.3 for more information). Constituent 1 is considered by the programme as ‘inorganic’ and therefore outside the training set domain and should be used with caution. Given the literature essentially indicates that the water solubility of phosphoric acid is > 850 g/L (ECHA, 2021) and/or testing was considered as “not scientifically necessary” due to low adsorption potential. It should be considered that the model prediction is essentially correct given the water solubility intrinsic relationship with partition coefficient and consequently the adsorption coefficient within the environmentally relevant pH range (4 to 9). A low value of Log Kow and consequently Log Koc, can be expected. The model can be extrapolated to substances outside the MW-fragment domain (as was done in the 372 substances outside the domain used in the model validation set. See QMRF title section 9.3 for more information). Expert judgement would indicate that the extrapolated predictions appear adequate for all structures at a screening level. Overall it would appear that the Log Kow Regression model is a better model for the target substance as it has greater coverage of the target substance and its constituent fragments – implicit within the model training set.

 

3. Uncertainty of the prediction and mechanistic domain:

The training set of the model has the following statistics and coefficients of determination:

MCI Methodology (no corrections, non-polar)

Training Set Statistics: number in dataset = 69 ; correlation coef (r2) = 0.967 ; standard deviation = 0.247 ; absolute deviation = 0.199

MCI Methodology (with corrections)

Training Set Statistics: number in dataset = 447 ; correlation coef (r2) = 0.900 ; standard deviation = 0.340 ; absolute deviation = 0.273

 

Log Kow to Log Koc Methodology (no corrections)

Training Set Statistics: number in dataset = 68 ; correlation coef (r2) = 0.877 ; standard deviation = 0.478; absolute deviation = 0.371

Log Kow to Log Koc Methodology (with corrections)

Training Set Statistics: number in dataset = 447 ; correlation coef (r2) = 0.855 ; standard deviation = 0.396 ; absolute deviation = 0.307

 

The combined training sets (of 516 substances) has the following statistics:

MCI Methodology

Total Training Set Statistics: number in dataset = 516 ; correlation coef (r2) = 0.916 ; standard deviation = 0.330 ; absolute deviation = 0.263

Log Kow to Log Koc Methodology

Total Training Set Statistics: number in dataset = 516 ; correlation coef (r2) = 0.860 ; standard deviation = 0.429 ; absolute deviation = 0.321

 

The model has been externally validated on a set of 158 (or 150) substances and the following statistics and coefficients of determination are presented:

Validation Set Statistics - MCI Methodology:

number in dataset = 158 ; correlation coef (r2) = 0.850 ; standard deviation = 0.583 ; absolute deviation = 0.459

Validation Set Statistics - Log Kow Methodology:

number in dataset = 150 ; correlation coef (r2) = 0.778 ; standard deviation = 0.679 ; absolute deviation = 0.494

 

Data for the training set are available via external validation (see attached QMRF prepared by the applicant for full citations).

The model is based on the thermodynamic relationship between surrogates chemical structure (group contribution) fragments and their chemical activity from first order molecular connectivity (surface area) indices and separately thermodynamic relationship with physicochemical properties, specifically correlation with n-octanol/water partitioning coefficients and substructure correction. In order to improve the model additional substances could be added to the model; new fragments and substructure corrections introduced. The model is non-proprietary and the training sets and validation sets can be downloaded from the internet. A summary of this information is presented by the applicant. For the substance, and consideration of the structural fragment domain it is considered that the Log Kow Regression sub-model had better domain applicability than MCI Regression sub-model.

Validity criteria fulfilled:

yes

Conclusions:

The results are adequate for the for the regulatory purpose.

Executive summary:

KOCWIN v2.00 (model publication: November 2012)

All predictions are based on the KOCWIN v2.00: Log Kow Regression sub-model due to greater domain applicability than the MCI Regression sub-model.

Koc range (all constituents): >= 0.3978 to <= 130.1 L/Kg

Log Koc range (all constituents): >= -0.4004 to <= 2.114

The range of constituents was: Log Koc = -0.4004 to 2.114 in three blocks, respectively.

The majority of constituents had Log Koc = ca. 1.0 to 1.4

The substance consists of blocks of constituents of predicted Log Kow < 4.0. This was subsequently confirmed by experimental measurement (OECD TG 117, 2021) which demonstrated a Log Kow < 3.0. Consequently, the substance is not expected to have significant adsorption potential in the environmentally relevant pH range (pH 4 to pH 9)

 

Adequacy of assessment of the (Q)SAR results.

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 contributing information to the environmental fate and transport and distribution assessment of the substance. The prediction is also supporting information 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 environmental toxicity and environmental fate testing.

Reference 2

Endpoint:

adsorption / desorption: screening

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance has a low octanol water partition coefficient and the adsorption potential of this substance is related to this parameter

the study does not need to be conducted because the physicochemical properties of the substance indicate that it can be expected to have a low potential for adsorption

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
In accordance with REACH Regulation (EC) No. 1907/2006 Annex VIII, column 2 section 9.3.1 the study does not need to be conducted if based on the physicochemical properties the substance can be expected to have a low potential for adsorption (e.g. the substance has a low octanol water partition coefficient). The substance possesses a measured Log Kow < 3.0 for all identified constituents and does not possess additional confounding properties (e.g. relevant ionisation potential) which affects partitioning behaviour within the environmentally relevant pH range (pH 4, 7 and 9). At these pH the substance constituents should exhibit maximum water solubility in addition. The applicant adapts the information requirement in accordance with the relevant testing strategy by providing measured and predicted QSAR log Pow for n-octanol/water partition coefficient and supporting QSAR predictions for log Koc in accordance with REACH Regulation (EC) 1907/2006: Annex XI Section 1.3, which demonstrates low potential for significant adsorption. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7a: Endpoint Specific Guidance, R.7.1.15, July 2017) the study does not need to be conducted.

Reason / purpose for cross-reference:

data waiving: supporting information

Reason / purpose for cross-reference:

data waiving: supporting information

Reason / purpose for cross-reference:

data waiving: supporting information

Description of key information

Log Koc, soil (range): >= 0.3978 to <= 130.1 L/Kg in three blocks, at 25 °C; ca. pH 7, QSAR Prediction - KOCWIN v2.00, 2021

All predictions are based on the KOCWIN v2.00: Log Kow Regression sub-model due to greater domain applicability than the MCI Regression sub-model.

The majority of constituents had Log Koc = ca. 1.0 to 1.4

The substance consists of blocks of constituents of predicted Log Kow < 4.0. This was subsequently confirmed by experimental measurement (OECD TG 117, 2021) which demonstrated a Log Kow < 3.0. Consequently, the substance is not expected to have significant adsorption potential in the environmentally relevant pH range (pH 4 to pH 9)

Additional information

QSAR Predictions KOCWIN v2.00 model, 2021 :

All predictions are based on the KOCWIN v2.00: Log Kow Regression sub-model due to greater domain applicability than the MCI Regression sub-model.

Koc range (all constituents): >= 0.3978 to <= 130.1 L/Kg

Log Koc range (all constituents): >= -0.4004 to <= 2.114

The range of constituents was: Log Koc = -0.4004 to 2.114 in three blocks, respectively.

The majority of constituents had Log Koc = ca. 1.0 to 1.4

The substance consists of blocks of constituents of predicted Log Kow < 4.0. This was subsequently confirmed by experimental measurement (OECD TG 117, 2021) which demonstrated a Log Kow < 3.0. Consequently, the substance is not expected to have significant adsorption potential in the environmentally relevant pH range (pH 4 to pH 9)

 

References for further information:

1. QMRF Title: KOCWIN v2.00: Soil Adsorption Coefficient (Koc), version 1.02, 04 March 2021

2. US EPA: KOCWIN v2.00; integrated within the Estimation Programme Interface (EPI) Suite programme for Microsoft Windows v4.1, November 2012 (model publication)

3. Applicant study reference: Log Kow (HPLC), OECD TG 117, GLP (2021)

In accordance with REACH Regulation (EC) No. 1907/2006 Annex VIII, column 2 section 9.3.1 the study does not need to be conducted if based on the physicochemical properties the substance can be expected to have a low potential for adsorption (e.g. the substance has a low octanol water partition coefficient). The substance possesses a measured Log Kow < 3.0 for all identified constituents and does not possess additional confounding properties (e.g. relevant ionisation potential) which affects partitioning behaviour within the environmentally relevant pH range (pH 4, 7 and 9). At these pH the substance constituents should exhibit maximum water solubility in addition. The applicant adapts the information requirement in accordance with the relevant testing strategy by providing measured and predicted QSAR log Pow for n-octanol/water partition coefficient and supporting QSAR predictions for log Koc in accordance with REACH Regulation (EC) 1907/2006: Annex XI Section 1.3, which demonstrates low potential for significant adsorption. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7a: Endpoint Specific Guidance, R.7.1.15, July 2017) the study does not need to be conducted.