Reaction products of ((5E)-5-ethylidenebicyclo[2.2.1]hept-2-ene and (5Z)-5-ethylidenebicyclo[2.2.1]hept-2-ene) and 2-methyl-1,3-butadiene, epoxidized

Adsorption / desorption

Link to relevant study record(s)

Reference

Endpoint:

adsorption / desorption: screening

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
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 ((5E)-5-ethylidenebicyclo[2.2.1]hept-2-ene and (5Z)-5-ethylidenebicyclo[2.2.1]hept-2-ene) and 2-methyl-1,3-butadiene, epoxidized using the model KOCWIN v2.00 for the endpoint: Soil Adsorption Coefficient (Koc)’ version 1.0; dated 01 March 2018.

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 1.0; 17 January 2018.

5. APPLICABILITY DOMAIN
See ‘any other information on results incl. tables’.
See QPRF attached: ‘QPRF Title: Substance: Reaction products of ((5E)-5-ethylidenebicyclo[2.2.1]hept-2-ene and (5Z)-5-ethylidenebicyclo[2.2.1]hept-2-ene) and 2-methyl-1,3-butadiene, epoxidized using the model KOCWIN v2.00 for the endpoint: Soil Adsorption Coefficient (Koc)’ version 1.0; dated 01 March 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 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.

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 1.0; 17 January 2018.
- 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: The result should be considered in relation to corresponding information presented and in accordance with the tonnage driven information requirements of REACH Regulation (EC) 1907/2006 in a weight of evidence.
Specifically the substance is hydrolytically unstable. The substance constituents have short hydrolytic half-lives (scale: hours at neutral pH, ambient temperatures, accelerated in acidic or basic pH conditions by catalytic hydrolysis) they would be considered as fulfilling the criteria for rapid (primary) degradability.
Provision of measured experimental log Koc has been determined as not technically possible under guideline OECD TG 121 HPLC method (under OECD TG 117 HPLC method of Koc that the test item was determined to be too unstable). It is also potentially not possible by other methods. Therefore, in accordance with the tonnage driven information requirements: the calculated method for Log Koc has been adopted.
The calculated predictions are indicative of a substance of low to moderate adsorption potential: blocks of Loc Koc in the range of 2.09 and 2.96. The rapidly formed primary hydrolysis products are of much lower adsorption potential in several blocks of log Koc: -0.042, 0.73 and 1.59, as the hydrolysis products become more water soluble.

Media:

soil

Type:

log Koc

Value:

>= 2.099 - <= 2.964 dimensionless

pH:

7

Temp.:

25 °C

Matrix:

Soil

Remarks on result:

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

Type:

Koc

Value:

>= 125.6 - <= 920.6 L/kg

pH:

7

Temp.:

25 °C

Matrix:

Soil

Remarks on result:

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

Transformation products:

yes

No.:

#1

No.:

#2

No.:

#3

No.:

#4

No.:

#5

No.:

#6

No.:

#7

No.:

#8

No.:

#9

No.:

#10

No.:

#11

No.:

#12

No.:

#13

No.:

#14

No.:

#15

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 ((5E)-5-ethylidenebicyclo[2.2.1]hept-2-ene and (5Z)-5-ethylidenebicyclo[2.2.1]hept-2-ene) and 2-methyl-1,3-butadiene, epoxidized using the model KOCWIN v2.00 for the endpoint: Soil Adsorption Coefficient (Koc)’ version 1.0; dated 01 March 2018.

 

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): >= 125.6 to <= 920.6 L/Kg

Log Koc range (all constituents): >= 2.099 to <= 2.964

The range of constituents was: Log Koc = 2.099 to 2.964 in two blocks, respectively.

The majority of constituents had Log Koc = 2.94

 

The substance constituents have short hydrolytic half-lives (scale: hours at neutral pH, ambient temperatures, accelerated in acidic or basic pH conditions by catalytic hydrolysis) they would be considered as fulfilling the criteria for rapid (primary) degradability.

 

Hydrolysis products have range of Log Koc = -0.0416, 0.7307 and 1.5901 in three blocks, respectively.

The majority of hydrolysis products had Log Koc = 1.5901

 

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 1.0; 17 January 2018 – section 5; indicates the substance (constituents):

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

(ii) There are no direct analogues (bicyclic epoxides) in the training (or validation) sets and there are no distinct epoxide group correction factors in the log Kow regression methodology. Such substances are treated as aliphatic ethers (with correction factor coefficient; maximum occurrence: 2). There are aromatic ether/carbonyls and anthracenes (multi-aromatics) in the training set for the Log Koc regression with correction factor coefficient. There is an aliphatic alcohol containing analogue in the training set (with coefficient; maximum occurrence: 1). Expert judgement indicates that there is limited domain applicability in the MCI model for the constituents. In addition, the hydrolysis products are technically out of MCI structural fragment domain as they contain more than the maximum number of aliphatic alcohol functions. They are however, within the Log Kow regression methodology domain as this primarily addresses the prediction by addressing the thermodynamic relationship between partitioning behaviour and the Koc. See QMRF section 4.2. Overall it would appear due to the lack of MCI and correction factor and lack of cyclic epoxide groups in the training set 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. Expert judgement would indicate that the substance constituent and its hydrolysis products are in the structural fragment domain of the Log Kow regression model.

 

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 its hydrolysis products, 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): >= 125.6 to <= 920.6 L/Kg

Log Koc range (all constituents): >= 2.099 to <= 2.964

The range of constituents was: Log Koc = 2.099 to 2.964 in two blocks, respectively.

The majority of constituents had Log Koc = 2.964

 

c

 

Hydrolysis products have range of Log Koc = -0.0416, 0.7307 and 1.5901 in three blocks, respectively.

The majority of hydrolysis products had Log Koc = 1.5901

The calculated predictions are indicative of a substance of low to moderate adsorption potential: blocks of Loc Koc in the range of 2.09 and 2.96. The rapidly formed primary hydrolysis products are of much lower adsorption potential in several blocks of log Koc: -0.042, 0.73 and 1.59, as the hydrolysis products become more water soluble.

 

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 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.

Description of key information

Log Koc = 2.099; KOCWIN v2.0

Key value for chemical safety assessment

Koc at 20 °C:

125.6

Additional information

The log Koc = 2.099 (Koc = 125.6 L/kg) used for assessment entity 1 (of 2) is based on the predicted Koc values of constituent 10 - 11 of the substance, using KOCWIN v2.0. Refer to the relevant QMRF and QPRF documents, and Section 0.4 of IUCLID for further information.