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Diss Factsheets

Administrative data

Endpoint:
partition coefficient
Type of information:
(Q)SAR
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
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

c1ccc(cc1)OCC(O)CN(CCN=C(C)CC(C)C)CCN=C(C)CC(C)C

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): 8.53

SMILES : c1ccc(cc1)OCC(O)CN(CCN=C(C)CC(C)C)CCN=C(C)CC(C)C
CHEM :
MOL FOR: C25 H43 N3 O2
MOL WT : 417.64
-------+-----+--------------------------------------------+---------+--------
TYPE| NUM | LOGKOW FRAGMENT DESCRIPTION| COEFF| VALUE
-------+-----+--------------------------------------------+---------+--------
Frag | 6 | -CH3 [aliphatic carbon] | 0.5473 | 3.2838
Frag | 8 | -CH2- [aliphatic carbon] | 0.4911 | 3.9288
Frag | 3 | -CH [aliphatic carbon] | 0.3614 | 1.0842
Frag | 2 | C [aliphatic carbon - No H, not tert] | 0.9723 | 1.9446
Frag | 1 | -OH [hydroxy, aliphatic attach] | -1.4086 | -1.4086
Frag | 1 | -N< [aliphatic attach] |-1.8323 | -1.8323
Frag | 6 | Aromatic Carbon | 0.2940 | 1.7640
Frag | 1 | -O- [oxygen, one aromatic attach] | -0.4664 | -0.4664
Frag | 2 | -N=C [aliphatic attach] | -0.001 | -0.002
Const | | Equation Constant | | 0.2290
-------+-----+--------------------------------------------+---------+--------
Log Kow = 8.5251

Experimental Database Structure Match:
Name : N,N'-DIMETHYLACETAMIDE
CAS Num : 000127-19-5
Exp Log P: -0.77
Exp Ref : HANSCH,C ET AL. (1995)

SMILES : CN(C)C(=O)(C)
CHEM :
MOL FOR: C4 H9 N1 O1
MOL WT : 87.12
-------+-----+--------------------------------------------+---------+--------
TYPE | NUM | LOGKOW FRAGMENT DESCRIPTION | COEFF | VALUE
-------+-----+--------------------------------------------+---------+--------
Frag | 3 | -CH3 [aliphatic carbon] | 0.5473 | 1.6419
Frag | 1 | -N< [aliphatic attach] |-1.8323 | -1.8323
Frag | 1 | -C(=O)N [aliphatic attach] |-0.5236 | -0.5236
Const | | Equation Constant | | 0.2290
-------+-----+--------------------------------------------+---------+--------
Log Kow = -0.4850


- 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:
study report
Title:
Unnamed
Year:
2018

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)
Deviations:
yes
Remarks:
A calculation method was applied because the partition coefficient could not be determined experimentally due to the substance being hydrolytically unstable in water
Principles of method if other than guideline:
Prediction software (KOWWIN v1.68) was used, according to the test guidance, because the test
material was found to be unstable in water and therefore formal testing was not possible.
GLP compliance:
no
Type of method:
calculation method (fragments)
Partition coefficient type:
octanol-water

Test material

Constituent 1
Chemical structure
Reference substance name:
1-(bis(2-(1,3-dimethylbutylideneamino)ethyl)amino)-3-phenoxypropan-2-ol
EC Number:
271-340-7
EC Name:
1-(bis(2-(1,3-dimethylbutylideneamino)ethyl)amino)-3-phenoxypropan-2-ol
Cas Number:
68541-07-1
Molecular formula:
C25H43N3O2
IUPAC Name:
1-(bis(2-(1,3-dimethylbutylideneamino)ethyl)amino)-3-phenoxypropan-2-ol
Test material form:
liquid

Study design

Analytical method:
other: Not applicable; prediction software was used instead

Results and discussion

Partition coefficient
Key result
Type:
log Pow
Partition coefficient:
ca. 8.53
Remarks on result:
other: predicted by KOWWIN

Applicant's summary and conclusion

Conclusions:
The logKow of the substance was estimated to be 8.53 using prediction software (KOWWIN v1.68)
because the substance is unstable in water.