[No public or meaningful name is available]

Adsorption / desorption

Administrative data

Endpoint:

adsorption / desorption: screening

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

January 2022

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 limited documentation / justification

Justification for type of information:

1. SOFTWARE
EPISuite (v4.00 - v4.11)(developed by the EPA’s Office of Pollution Prevention Toxics and Syracuse Research Corporation (SRC))

2. MODEL (incl. version number)
KOCWIN v2.00 (September 2010)

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
SMILES: Cc1cccc(NC(=O)c3cc(cc(c3)S(=O)(=O)Nc4cccc(C)c4)C(=O)Nc2cccc(C)c2)c1
logKow entered: 4.3 (at 25 ºC)

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: logKoc
- Unambiguous algorithm: 2 different methods are used (using first-order molecular connectivity index (MCI) and using logKow)
- Defined domain of applicability: the maximum number of instances of a correction factor and the molecular weight
The model domain gives minimum and maximum values for molecular weight as follows:
Training Set Molecular Weights:
Minimum MW:  32.04
Maximum MW:  665.02
Average MW:  224.4

Validation Molecular Weights:
Minimum MW:  73.14
Maximum MW:  504.12
Average MW:  277.8

Currently there is no universally accepted definition of model domain.  However, users may wish to consider the possibility that log Koc estimates are less accurate for compounds outside the MW range of the training set compounds, and/or that have more instances of a given fragment than the maximum for all training set compounds.  It is also possible that a compound may have a functional group(s) or other structural features not represented in the training set, and for which no fragment coefficient or correction factor was developed.

- Appropriate measures of goodness-of-fit and robustness and predictivity: KOCWIN is a wel-known program to estimate the adsorption coefficient of organic compounds. Overall, the MCI methodology is somewhat more accurate than the logKow methodology, although both methods yield good results.  If the Training datasets are combined into one dataset of 516 compounds (69 having no corrections plus 447 with corrections), the MCI methodology has an r^2, standard deviation and average deviation of 0.916, 0.330 and 0.263, respectively, versus 0.86, 0.429 and 0.321 for the logKow methodology.
The following journal article explains the MCI prediction methodology and its use:
(1) Meylan, W., P.H. Howard and R.S. Boethling, "Molecular Topology/Fragment Contribution Method for Predicting Soil Sorption Coefficients", Environ. Sci. Technol. 26: 1560-7 (1992).
Journal abstract: "The first-order molecular connectivity index (MCI) has been successfully used to predict soil sorption coefficients (Koc) for nonpolar organics, but extension of the model to polar compounds has been problematic.  To address this, we developed a new estimation method based on MCI and series of statistically derived fragment contribution factors for polar compounds. After developing an extensive database of measured Koc values, we divided the dataset into a training set of 189 chemicals and an independent validation set of 205 chemicals.  Two linear regressions were then performed.  First, measured log Koc values for nonpolar compounds in the training set were correlated with MCI.  The second regression was developed by using the deviations between measured log Koc and the log Koc estimated with the nonpolar equation and the number of certain structural fragments in the polar compounds.  The final equation for predicting log Koc accounts for 96% and 86% of the variation in the measured values for the training and validation sets, respectively.  Results also show that the model outperforms and covers a wider range of chemical structures than do models based on octanol-water partition coefficients (Kow) or water solubility."
 
- Mechanistic interpretation: for the logKow method, 674 compounds were selected and eventually divided into a training set of 516 compounds and a validation set of 158 compounds.  The training set was divided further into a dataset of 69 non-polar organics and 447 polar organics (same as previously described in Meylan et al, 1992).  For the current model development, the non-polar dataset is designated as compounds having "No Correction Factors" while the polar compounds are designated as compounds "Having Correction factors".
For the MCI method, the same methodology as described in (Meylan et al, 1992) was used to develop the QSAR equations.  Two separate regressions were performed.  The first regression related log Koc of non-polar compounds to the first-order MCI.  As noted above, non-polar compounds are now designated as "compounds having no correction factors" which simply means the MCI descriptor alone can adequately predict the Koc.  Measured log Koc values were fit to a simple linear equation of the form:
 log Koc  = a MCI  + b
where a and b are the coefficients fit by least-square analysis (69 compounds used for this regression).
The second regression included the 447 compounds having correction factors.  Correction factors are specific chemical classes or structural fragments.  The regression coefficients were derived via multiple linear regression of the correction descriptors to the residual error of the prediction from the non-polar equation.

5. APPLICABILITY DOMAIN
- The MW of the substance is within the MW range of the training set and the instances of a given fragment are within the maximum for all training set compounds in the model domain (see attached full study reports).

6. ADEQUACY OF THE RESULT
The estimations show that the substance has high adsorption potential. A follow-up batch equilibrium test (OECD 106) will be conducted. In accordance with REACH Guidance R.7.1.15.4, if estimation methods (like HPLC OECD 121) are not appropriate (e.g. because the substance is a surfactant or ionisable at environmentally-relevant pH), then a batch equilibrium test may need to be considered at the 10 tonnes per year band, and would be essential at the 100 tonnes per year band. As Pergafast 425 is both surface active and ionizable, a batch equilibrium test (OECD 106) is required and will be performed without a testing proposal.

Data source

Reference

Reference Type:

other: QSAR calculation logKoc

Title:

Unnamed

Year:

2022

Report date:

2022

Materials and methods

Principles of method if other than guideline:

Used model: KOCWIN v2.00, as part of EPISuite (v4.00 - v4.11)(developed by the EPA’s Office of Pollution Prevention Toxics and Syracuse Research Corporation (SRC))

GLP compliance:

no

Type of method:

other: KOCWIN v2.00

Test material

Test material information

Constituent 1

Reference substance name:

N1,N3‐bis(3‐methylphenyl)‐5‐[(3‐methylphenyl)sulfamoyl]benzene‐1,3‐dicarboxamide

Cas Number:

2375645-78-4

Molecular formula:

C29 H27 N3 O4 S

IUPAC Name:

N1,N3‐bis(3‐methylphenyl)‐5‐[(3‐methylphenyl)sulfamoyl]benzene‐1,3‐dicarboxamide

Specific details on test material used for the study:

molecular weight = 513.6

Study design

Test temperature:

25 ºC (for the logKow method)

Batch equilibrium or other method

Computational methods:

Two methods are used in KOCWIN:
- based on the octanol/water partition coefficient
- based on the first-order molecular connectivity index (MCI)

Results and discussion

Adsorption coefficient

Adsorption coefficient 1

Sample No.:

#1

Type:

log Koc

Value:

4.2

Temp.:

25 °C

Remarks on result:

other: estimated by QSAR (MCI)

Adsorption coefficient 2

Sample No.:

#1

Type:

log Koc

Value:

2.9 - 3.7

Temp.:

25 °C

Remarks on result:

other: estimated value by QSAR (with measured and estimated logKow)

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Remarks:

The MW of the substance is within the MW range of the training set and the instances of a given fragment are within the maximum for all training set compounds in the model domain.

Conclusions:

KOCWIN v2.00, as part of EPISuite was used to estimate the logKoc. Two different methods were used in the model, resulting in logKoc = 4.2 (MCI) and ranging from 2.9 to 3.7 (dependent on a measured or estimated logKow).
These values are estimations and show that the substance has high adsorption potential. In accordance with REACH Guidance R.7.1.15.4, if estimation methods (like HPLC OECD 121) are not appropriate (e.g. because the substance is a surfactant or ionisable at environmentally-relevant pH), then a batch equilibrium test may need to be considered at the 10 tonnes per year band, and would be essential at the 100 tonnes per year band. As Pergafast 425 is both surface active and ionizable, a batch equilibrium test (OECD 106) is required and will be performed without a testing proposal.