N-cyclohexylbenzothiazole-2-sulfenamide

Adsorption / desorption

Link to relevant study record(s)

Reference

Endpoint:

adsorption / desorption: screening

Remarks:

adsorption

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
Individual model KOCWIN included in the Estimation Programs Interface (EPI) Suite.

2. MODEL (incl. version number)
KOCWIN v2.00 included in EPISuite v 4.11, 2000-2015.

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
A SMILES NOTATION (n(c(c(s1)ccc2)c2)c1SNC(CCCC3)C3) was entered in the initial data entry screen. In the structure window, the molecular weight, structural formula and the structure of the input SMILES notation is shown.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
a. Defined endpoint: Organic carbon partition coefficient, given as log Koc.
b. Dependent variable: KOCWIN estimates log Koc with two separate estimation methodologies:
(1) Estimation using first order Molecular Connecitivity Index (MCI),
(2) Estimation using log Kow (octanol-water partition coefficient)
c. Algorithm:
Log Koc according to MCI method is calculated using the formula:
log Koc = 0.5213 MCI + 0.60 + ΣPfN
(ΣPfN is the sum of all relevant correction factor coefficients multiplied by the number (N) of that factor in each chemical structure)
Log Koc according to the log Kow method is calculated using two formulas (depending on the polarity of the substance):
log Koc = 0.8679 log Kow - 0.0004 (Non-polar substances)
log Koc = 0.55313 log Kow + 0.9251 + ΣPfN (polar substances)

d. Descriptor values:
Log Kow method:
For estimation of log Koc according to log Kow method an experimentally determined log Kow of 5.0 was used (Currenta, 2010).

e. Applicability domain: The minimum and maximum values for molecular weight are the following:
Training Set Molecular Weights: 32.04-665.02 g/mol,
Validation Set Molecular Weights: 27.03-991.15 g/mol

f. Statistics for goodness-of-fit:

Statistical accuracy of MCI methodology for training and validation set:
i. Training without corrections:
Number: 69
R^2 correction coefficient: 0.967
Standard deviation (log Koc): 0.247
Average deviation (log Koc): 0.199

ii. Training with corrections:
Number: 447
R^2 correction coefficient: 0.900
Standard deviation (log Koc): 0.340
Average deviation (log Koc): 0.273

iii. Validation data set:
Number: 158
R^2 correction coefficient: 0.850
Standard deviation (log Koc): 0.583
Average deviation (log Koc): 0.459

Statistical accuracy of Log Koc methodology:
i. Training without corrections:
Number: 68
R^2 correction coefficient: 0.877
Standard deviation: 0.478
Average deviation: 0.371

ii. Training with corrections:
Number: 447
R^2 correction coefficient: 0.855
Standard deviation (log Koc): 0.396
Average deviation (log Koc): 0.307

iii. Validation data set:
Number: 150
R^2 correction coefficient: 0.778
Standard deviation (log Koc): 0.679
Average deviation (log Koc): 0.494

g. Mechanistic interpretation: Log Koc is estimated based on the likeliness of a substance for sorption to surfaces of soil/sediment particles. This characteristic is triggered by lipophilic character of substances but may be modified by certain molecular fragments that need to be considered by application of correction factors. The Log Koc is a physical inherent property used extensively to describe a chemical’s likeliness to adsorb to organic carbon.
h. The uncertainty of the prediction (OECD principle 4): N-cyclohexylbenzothiazole-2-sulphenamide is not highly complex and the rules applied for the substance appear appropriate. An individual uncertainty for the investigated substance is not available.

5. APPLICABILITY DOMAIN
a. Descriptor domains:
i. Molecular weights: With a molecular weight of 264.41 g/mol the substance is within the range of the training set (32 - 665 g/mol) as well as in the range of the validation set (27 -– 991 g/mol).
ii. Structural fragment domain: Regarding the structure of N-cyclohexylbenzothiazole-2-sulphenamide the fragment descriptors found by the program are complete and listed in Appendix D (KOCWIN Fragment and Correction Factor descriptors). For log Koc estimation according to MCI method no fragment descriptors were applied. For estimation of log Koc according to log Kow method the log Kow of 5 (experimentally determined, Currenta, 2010) was used.
iii. Mechanism domain: No information available.
iv. Metabolic domain: Not relevant.
b. Structural analogues: No information available
i. Considerations on structural analogues: No information available

6. ADEQUACY OF THE RESULT
a. Regulatory purpose: The data may be used under any regulatory purpose.
b. Approach for regulatory interpretation of the model result: If no experimental data are available, the estimated value may be used to fill data gaps needed for hazard and risk assessment, classification and labelling and PBT / vPvB assessment. Further the value is used for other calculations.
c. Outcome: The prediction of organic carbon partition coefficient yields a useful result for further evaluation.
d. Conclusion: The result is considered as useful for regulatory purposes.

Guideline:

other: REACH guidance QSARs R6, May/July 2008

Principles of method if other than guideline:

Estimation Program Interface EPI-Suite version 4.11: KOCWIN (v2.01) for the estimation of the organic carbon-normalized sorption coefficient for soil and sediment (Koc).
The Estimation Program Interface was developed by the US Environmental Agency's Office of Pollution Prevention and Toxics, and Syracuse Research Corporation (SRC). © 2000 - 2012 U.S. Environmental Protection Agency for EPI SuiteTM (Published online in November 2012).

Calculation according to Sabljić 1995 (A. Sabljić, H. Güsten, H. Verhaar, J. Hermens, Chemosphere 1995, 31, 4489-4514: QSAR modelling of soil sorption. Improvements and systematics of log Koc vs. logKow correlations)

Calculation according to Gerstl 1990 (Z. Gerstl, Journal of Contaminant Hydrology 1990, 6, 357-375: Estimation of organic chemical sorption by soils)

GLP compliance:

no

Type of method:

other: Estimation

Sample No.:

#4

Type:

log Koc

Value:

3.62

Remarks on result:

other: calculated Sabljić, 1995

Sample No.:

#3

Type:

log Koc

Value:

3.56

Remarks on result:

other: calculated, Gerstl 1990

Sample No.:

#2

Type:

log Koc

Value:

4.125

Remarks on result:

other: calculated by EPI Suite version 4.11 (KOCWIN); MCI method

Key result

Sample No.:

#1

Type:

log Koc

Value:

3.333

Remarks on result:

other: calculated by EPI Suite version 4.11 (KOCWIN); logKow method

Sample No.:

#2

Phase system:

other: Koc

Value:

13 350 L/kg

Remarks on result:

other: calculated by EPI Suite version 4.11 (KOCWIN); MCI method

Key result

Sample No.:

#1

Phase system:

other: Koc

Value:

2 154 L/kg

Remarks on result:

other: calculated by EPI Suite version 4.11 (KOCWIN); logKow method

Validity of the model:

1. Defined Endpoint: Organic carbon partition coefficient, given as logarithmic Koc and Koc

2. Unambigous algorithm: The molecule is first classified as a polar substance. Based on structure of the molecule, the following fragments were applied: 1 Nitrogen-to-Cycloalkane (aliphatic). The number of times of the fragments that occurs in the structure of the substance applied by the program is verified. For estimation of logKoc according to the logKow method an experimentally determined log Kow of 5.0 was used (Currenta, 2010).

3. Applicable domain: With a molecular weight of 264.41 g/mol the substance is within the range of the training set (32 - 665 g/mol) as well as in the validation set (27 - 991 g/mol). Regarding the structure of N-cyclohexylbenzothiazole-2-sulphenamide, the fragment descriptors found by the program are complete.

4a. Statistical characteristics (MCI method): N training set without corrections = 69; N training set with correction = 447; N validation set = 158; Correction coefficient of the total training set without corrections r² = 0.967; Correlation coefficient of the total training set with corrections r² = 0.900; Correlation coefficient of the total validation set r² = 0.850.

4b. Statistical characteristics (Kow method): N training set without corrections = 68; N training set with correction = 447; N validation set = 150; Correction coefficient of the total training set without corrections r² = 0.877; Correlation coefficient of the total training set with corrections r² = 0.855; Correlation coefficient of the total validation set r² = 0.778.

5. Mechanistic interpretation: Log Koc is estimated based on the likeliness of a substance for sorption to surfaces of soil/sediment particles. The log Koc is a physical inherent property used extensively to describe a chemical's likeliness to adsorb to organic carbon.

6. Adequacy of prediction: The result for N-cyclohexylbenzothiazole-2-sulphenamide falls within the applicability domain described above and the estimation rules applied for the substance appears appropriate.

Validity criteria fulfilled:

not applicable

Conclusions:

The QSAR determination of the carbon partition coefficient for N-cyclohexylbenzothiazole-2-sulphenamide using the model KOCWIN included in the Estimation Program Interface (EPI) Suite v4.11 revealed values of 2154 L/kg (logKow method) and 13350 L/kg (MCI method), corresponding to a logarithmic organic carbon partition coefficient of 4.1254 (MCI method) and 3.3332 (logKow method) for the unaffected molecule of the substance as any decomposition (e.g. hydrolysis) of the substance is not taken into account by the program.

Two additional calculation models revealed a logarithmic organic carbon partition coefficient of 3.62 (Sabljić 1995 ) and 3.561 (Gerstl 1990).

As a worst-case assumption, the lowest log Koc of 3.3332 (Koc = 2154 L/kg) is used for further exposure assessment of PNEC in sediment and soil using EPM method.

Executive summary:

The organic carbon partition coefficient (Koc) for N-cyclohexylbenzothiazole-2-sulphenamide  was predicted using the QSAR calculation of the Estimation Program Interface (EPI) Suite v 4.11 and two additional calculation models. The Koc was estimated to be 2154 L/kg (logKow method) and 13350 L/kg (MCI method), corresponding to a logarithmic organic carbon partition coefficient of 4.1254 (MCI method) and 3.3332 (logKow method). The results relate to the unaffected molecule of the substance as any decomposition (e.g. hydrolysis) of the substance is not taken into account by the program.

Two additional calculation models revealed a logarithmic organic carbon partition coefficient of 3.62 (Sabljić 1995 ) and 3.561 (Gerstl 1990).

As a worst-case assumption, the lowest log Koc of 3.3332 is used for further exposure assessment of PNEC in sediment and soil using EPM method.

Description of key information

The organic carbon partition coefficient (Koc) for N-cyclohexylbenzothiazole-2-sulphenamide  was predicted using the QSAR calculation of the Estimation Program Interface (EPI) Suite v 4.11 and two additional calculation models. The Koc was estimated to be 2154 L/kg (logKow method) and 13350 L/kg (MCI method), corresponding to a logarithmic organic carbon partition coefficient of 4.1254 (MCI method) and 3.3332 (logKow method). The results relate to the unaffected molecule of the substance as any decomposition (e.g. hydrolysis) of the substance is not taken into account by the program.

Two additional calculation models revealed a logarithmic organic carbon partition coefficient of 3.62 (Sabljić 1995 ) and 3.561 (Gerstl 1990).

As a worst-case assumption, the lowest log Koc of 3.3332 is used for further exposure assessment of PNEC in sediment and soil using EPM method.

The log Koc of the described metabolites of CBS, such as MBT, MBTS, BT, and MeSBT, are mostly higher than 3 indicating moderate to strong potential for soil and sediment adsorption as the same as CBS. Only BTon (estimated log Koc of 1.93) and MeBT (estimated log Koc of 2.30) have very low adsorption potential.

Key value for chemical safety assessment

Koc at 20 °C:

2 154

Additional information

In the EU-risk assessment, log Koc was estimated from log Pow, which was an experimental result from Monsanto (1980). The Monsanto study for log Pow is assigned to be a reliability of 3 in up-to-date assessment due to inappropriate experimental method used. The newly determined log Pow (Currenta, 2010) is used here for further estimation of log Koc. As a worst-case assumption, the lowest log Koc of 3.3332 is used for further exposure assessment of PNEC in sediment using EPM method.

According to the classification scheme of Swann et al. (1983) estimated log Koc-values 3.56 -4.15 indicates a high sorption potential to soil and sediment and suggests a slow migration potential to ground water.