α,α,α,2-tetrachlorotoluene

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

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

EPIsuite 4.1 2012

2. MODEL (incl. version number)

KOWWIN 1.68

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL

Clc1ccccc1C(Cl)(Cl)Cl

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL

- Defined endpoint: octanol water partiton coeffcient
- Unambiguous algorithm: yes, the algorithm is based on an atom/fragment contribution method
The  log P  = Σ(fini ) + Σ(cjnj ) + 0.229 where where Σ(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); Σ(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) and 0.229 is the linear equation constant.

- Defined domain of applicability: 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.

- Appropriate measures of goodness-of-fit and robustness and predictivity: The training set statistics are as follows:
  number in dataset      = 2447
  correlation coef (r2)  = 0.982
  standard deviation     = 0.217
  absolute deviation     = 0.159
  avg Molecular Weight   = 199.98

The training set estimation error shows >95% of estimates are within 0.5 of the measured values of the training set
Training Set Estimation Error:
within <= 0.10  -  45.0%
within <= 0.20  -  72.5%
within <= 0.40  -  92.4%
within <= 0.50  -  96.4%
within <= 0.60  -  98.2%

KOWWIN has been tested on an external validation dataset of 10,946 compounds (compounds not included in the training set).  The validation set includes a diverse selection of chemical structures that rigorously test the predictive accuracy of any model.  It contains many chemicals that are similar in structure to chemicals in the training set, but also many chemicals that are different from and structurally more complex than chemicals in the training set.

Total Validation Set Statistics:
  number in dataset      = 10946
  correlation coef (r2)  = 0.943
  standard deviation     = 0.479
  absolute deviation     = 0.356
  avg Molecular Weight   = 258.98

Validation Set Estimation Error:
within <= 0.20  -  39.6%
within <= 0.40  -  66.0%
within <= 0.50  -  75.6%
within <= 0.60  -  82.5%
within <= 0.80  -  91.6%
within <= 1.00  -  95.6%
within <= 1.20  -  97.7%
within <= 1.50  -  99.1%

- Mechanistic interpretation: nort relevant for intrinsic pysical properties of substances

5. APPLICABILITY DOMAIN

- Descriptor domain: The substances falls within the molecular weight range of the training and validation datasets, close to the mean MW of both sets. The substance only contains molecular fragments contained in the model training set.
- Structural and mechanistic domains:

Log Kow(version 1.68 estimate): 4.54

SMILES : CLc1ccccc1C(CL)(CL)CL
CHEM :
MOL FOR: C7 H4 CL4
MOL WT : 229.92
-------+-----+--------------------------------------------+---------+--------
TYPE | NUM | KOW FRAGMENT DESCRIPTION | COEFF | VALUE
-------+-----+--------------------------------------------+---------+--------
Frag | 1 | C [aliphatic carbon - No H, not tert] | 0.9723 | 0.9723
Frag | 3 | -CL [chlorine, aliphatic attach] | 0.3102 | 0.9306
Frag | 6 | Aromatic Carbon | 0.2940 | 1.7640
Frag | 1 | -CL [chlorine, aromatic attach] | 0.6445 | 0.6445
Const | | Equation Constant | | 0.2290
-------+-----+--------------------------------------------+---------+--------
Log Kow = 4.5404

- Similarity with analogues in the training set: The substance only contains molecular fragments contained in the model training set.


6. ADEQUACY OF THE RESULT
The result can be considered adequate for risk assessment purposes as the prediction and model fulfil the OECD principlesfor QSAR.

Data source

Reference

Reference Type:

other: experimental database

Title:

EPISuite 4.1 KOWWIN Program v 1.68

Author:

US EPA

Year:

2012

Bibliographic source:

http://www.epa.gov/opptintr/exposure/pubs/episuitedl.htm

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The partition coefficient value has been calculated using the KOWWIN 1.68 QSAR, part of the EPIWIN 4.1 Suite.

Test material

Test material information

Constituent 1

Reference substance name:

α,α,α,2-tetrachlorotoluene

EC Number:

218-377-7

EC Name:

α,α,α,2-tetrachlorotoluene

Cas Number:

2136-89-2

Molecular formula:

C7H4Cl4

IUPAC Name:

1-chloro-2-(trichloromethyl)benzene

Results and discussion

Partition coefficient

Type:

log Pow

Partition coefficient:

4.54

Temp.:

25 °C

Remarks on result:

other: QSAR (EPIWIN 4.1)

Applicant's summary and conclusion

Conclusions:

The log Pow of the test item is 4.54 at 25°C according to QSAR estimation (EPIWIN 4.10).