(S)-(4,5-dihydro-5-thioxo-1,3,4-thiadiazol-2-yl) benzenecarbothioate

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

16 FEB 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 adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE
OECD QSAR toolbox v4.5

2. MODEL (incl. version number)
KOWWIN v1.69

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
Sc1nnc(SC(=O)c2ccccc2)s1

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Atom/fragment contribution values, used to estimate the log octanol-water partition coefficient (log P) of organic compounds, have been determined for 130 simple chemical substructures by a multiple linear regression of 1120 compounds with measured log P values. An additional 1231 compounds were used to determine 235 “correction factors” for various substructure orientations. The log P of a compound is estimated by simply summing all atom/fragment contribution values and correction factors occurring in a chemical structure. For the 2351 compound training set, the correlation coefficient (r²) for the estimated vs measured log P values is 0.98 with a standard deviation (SD) of 0.22 and an absolute mean error (ME) of 0.16 log units. This atom fragment contribution (AFC) method was then tested on a separate validation set of 6055 measured log P values that were not used to derive the methodology and yielded an r² of 0.943, an SD of 0.408, and an ME of 0.31. The method is able to predict log P within f 0.8 log units for over 96% of the experimental dataset of 8406 compounds. Because of the simple atom/fragment methodology, “missing fragments” (a problem encountered in other methods) do not occur in the AFC method. Statistically, it is superior to other comprehensive estimation methods.

5. APPLICABILITY DOMAIN
The applicability domain is described by the range of the molecular weight of chemicals in the training set as well as the identification and number of instances of a given fragment in any single compound. Additionally, the applicability domain is extended by inclusion of substructures larger or more complex than "atoms" to improve log P values estimates; hence, correction factors were added to the AFC method. The correction factors are values derived from the differences between the log P estimates from atoms alone and the measured log P values. The correction factors have two main groupings: first, factors involving aromatic ring substituent positions and second, miscellaneous factors. In general, the correction factors are values for various steric interactions, hydrogen-bondings, and effects from polar functional substructures. Individual correction factors were selected through a tedious process of correlating the differences (between log P estimates from atom/fragments alone and measured log P values) with common substructures.
Currently there is no universally accepted definition of model domain. However, users may wish to consider the possibility that log P 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 was developed. These points should be taken into consideration when interpreting model results. The predicted substance falls into the MW range of the training set compounds. Thus, it is considered to be in the applicability domain of this model.

Guideline:

other: REACH guidance on QSARs Chapter R.6

Version / remarks:

May 2008

Principles of method if other than guideline:

Software tool(s) used including version: OECD QSAR toolbox v4.5, EPI Suite v4.11
- Model(s) used: KOWWIN v1.69
- Model description:
Atom/Fragment Contribution (AFC (method)
KOWWIN uses a "fragment constant" methodology to predict log Kow. In a "fragment constant" method, a structure is divided into fragments (atom or larger functional groups) and coefficient values of each fragment or group are summed together to yield the log Kow estimate. KOWWIN’s methodology is known as an Atom/Fragment Contribution (AFC) method. Coefficients for individual fragments and groups were derived by multiple regression of 2447 reliably measured log Kow values. Correction factors were developed to be able to consider larger or more complex substructures than the fragments (“atoms”). log Kow = (fini) + (cjnj) + 0.229 (num = 2447, r2= 0.982, std. dev. = 0.217, mean error = 0.159) Where: 1)(fini) is the summation of fi (the coefficient for each atom/fragment) times ni (the number of times the atom/fragment occurs in the structure) 2)(cjnj) is the summation of cj (the coefficient for each correction factor) times nj (the number of times the correction factor occurs (or is applied) in the molecule).
[1]SMILES -- The only data required for KOWWIN to estimate log P is the chemical structure of the compound. The chemical structure is entered into the program as a SMILES notation.
[2]Fragments -- The structure is divided into fragments (atom or larger functional groups).
[3]Correction factors -- The correction factors were derived from a multiple linear regression that correlated differences between the experimental log Kow and the log Kow estimated by the initial equation [log Kow = (fini) + b; where b is the linear equation constant] with the correction factor descriptors.
- Justification of QSAR prediction: see field 'Justification for type of information'.

Type of method:

calculation method (fragments)

Partition coefficient type:

octanol-water

Specific details on test material used for the study:

Sc1nnc(SC(=O)c2ccccc2)s1

Key result

Type:

log Pow

Partition coefficient:

2.05

Temp.:

25

Remarks on result:

other: pH not specified, assumed to be neutral

Log Kow(version 1.69 estimate): 2.05
SMILES : Sc1nnc(SC(=O)c2ccccc2)s1
CHEM :
MOL FOR: C9 H6 N2 O1 S3
MOL WT : 254.34
-------+-----+--------------------------------------------+---------+--------
TYPE | NUM | LOGKOW FRAGMENT DESCRIPTION | COEFF | VALUE
-------+-----+--------------------------------------------+---------+--------
Frag | 8 | Aromatic Carbon | 0.2940 | 2.3520
Frag | 1 | -S- [aliphatic sulfur,one aromatic attach]| 0.0535 | 0.0535
Frag | 1 | Aromatic Sulfur | 0.4082 | 0.4082

Frag | 2 | Aromatic Nitrogen [5-member ring] |-0.5262 | -1.0524
Frag | 1 | -SH [thiol, aromatic attach] | 0.6925 | 0.6925
Frag | 1 | -C(=O)-S [thioester, aromatic attach] |-0.3500**| -0.3500
Factor| 1 | 1,3,4-Thiadiazole ring (non-fused) |-0.9800 | -0.9800
Factor| 1 | -C(=O)-S-aromatic correction | 0.7000 | 0.7000
Const | | Equation Constant | | 0.2290
-------+-----+--------------------------------------------+---------+--------
NOTE | | An estimated coefficient (**) used |
-------+-----+--------------------------------------------+---------+--------
Log Kow = 2.0528

Conclusions:

The log Pow of test item was calculated to be 2.05 using the US- EPA software KOWWIN v.1.69.

Executive summary:

The estimation of partition coefficient was done using the software KOWWIN v.1.69 implemented in EPIWIN program. The partition coefficient of test item was calculated to be 2.05. The prediction was in the applicability domain of the model.

Description of key information

The estimation of partition coefficient was done using the software KOWWIN v.1.69 implemented in EPIWIN program. The partition coefficient of the test item was calculated to be 2.05. The prediction was in the applicability domain of the model.

Key value for chemical safety assessment

Log Kow (Log Pow):

2.05

at the temperature of:

25 °C