Dialkyl C18 and C18-unsaturated phosphonates

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE:
--------------------
EPISUITE
MiLOGP
Sparc
Vega

2. MODEL (incl. version number)
----------------------------------------
KOWWIN v 1.68
MiLOGP
Sparc v 5.1
Vega v 1.14

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
-----------------------------------------------------------------------------------
Smiles
C(=CCCCCCCCCOP(=O)OCCCCCCCCC=CCCCCCCCC)CCCCCCCC
C(=CCCCCCCCCOP(=O)OCCCCCCCCCCCCCCCCCC)CCCCCCCC
C(=CCC=CCCCCCCCCOP(=O)OC)CCCCC
C(CCCCCCCCCCCCCCC)OP(=O)OC
C(=CCCCCCCCCOP(=O)OC)CCCCCCCC
C(CCCCCCCCCCCCCCCCC)OP(=O)OC
C(=CCC=CCCCCCCCCOP(=O)OCCCCCCCCC=CCCCCCCCC)CCCCC
C(CCCCCCCCCCCCCCCCC)OP(=O)OCCCCCCCCCCCCCCCCCC
C(CCCCCCCCCCCCCCCCC)OP(=O)OCCCCCCCCCCC
C(=CCCCCCCCCO)CCCCCCCC

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
-----------------------------------------------------------
- Defined endpoint: Yes for all the models used, the endpoint calculated is Log Kow
- Unambiguous algorithm: Yes for KOWWIN and MiLOGP
- Defined domain of applicability: Yes for KOWWIN and Vega
- Appropriate measures of
goodness-of-fit Yes for KOWWIN, MiLOGP and Sparc
robustness No information available for all the models used
predictivity: No information available for all the models used
- Mechanistic interpretation: Yes for KOWWIN and MiLOGP

5. APPLICABILITY DOMAIN
----------------------------------
- Descriptor domain: KOWWIN 158 structural fragments
MiLOGP 35 small simple "basic" fragments and 185 larger fragments.
Sparc no information available
Vega no information available

- Structural and mechanistic domains: The structural fragments used for partition coefficient estimation with KOWWIN are all included in the training and the validation set of this program. No detail about the structural fragments is available for the others QSAR used.
For KOWWIN all the molecular weight of the compounds tested are included in the molecular range of the training set. But the numbers of a specific fragment obtained for some predictions are higher than the number of this fragment in the training set. As such, the prediction obtained for the following compounds is considered to be out of the applicability domain: di((Z)-octadec-9-en-1-yl) phosphonate, (Z)-octadec-9-en-1-yl octadecyl phosphonate, (Z)-octadec-9-en-1-yl ((9Z,12Z)-octadeca-9,12-dien-1-yl) phosphonate, diOctadecyl phosphonate and Octadecyl undecyl phosphonate.
Two compounds are included in the applicability domain of VEGA: (Z)-methyl octadec-9-en-1-yl phosphonate for MlogP model and (Z)-octadec-9-en-1-ol for LOGP and MlogP models. Indeed, their AD index is equal to 0.85

- Similarity with analogues in the training set: For Vega, ionly for the moderate similarity with analogues in the training set for the following compounds: di((Z)-octadec-9-en-1-yl) phosphonate, (Z)-octadec-9-en-1-yl octadecyl phosphonate, (Z)-octadec-9-en-1-yl ((9Z,12Z)-octadeca-9,12-dien-1-yl) phosphonate, diOctadecyl phosphonate, Octadecyl undecyl phosphonate and (Z)-octadec-9-en-1-ol. No information is available for the QSAR used.

6. ADEQUACY OF THE RESULT
---------------------------------------
All QSAR model are scientifically valid.
All the compounds don't falls within the applicability domain of the QSAR models, but the information provided by the 7 programs used are considered relevante for a weight of evidence approach.
The Log Kow is a required endpoint for Reach registration. Therefore, this endpoint give information about the potential of bioaccumulation of coumpounds.

Principles of method if other than guideline:

Qsar estimations

GLP compliance:

no

Type of method:

calculation method (fragments)

Partition coefficient type:

octanol-water

Key result

Type:

log Pow

Partition coefficient:

> 5.19

Temp.:

20 °C

Remarks on result:

other: pH not available

Chemical name (IUPAC)	KOWWIN	Sparc	MiLOG P	Vega
				LOGP	ALOG P	MLOG P
di((Z)-octadec-9-en-1-yl) phosphonate	15.13	16.293	9.98	13.77	14.31	9.5
(Z)-octadec-9-en-1-yl octadecyl phosphonate	15.13	16.668	10.05	13.98	14.76	9.6
Methyl ((9Z,12Z)-octadeca-9,12-dien-1-yl) phosphonate	6.79	9.099	5.51	5.42	6.6	5.19
Methyl hexadecyl phosphonate	6.23	8.827	5.71	4.87	6.57	5.83
(Z)-methyl octadec-9-en-1-yl phosphonate	7.00	8.986	6.23	5.63	7.04	6.19
Methyl octadecyl phosphonate	7.22	9.733	6.72	5.85	7.48	6.3
(Z)-octadec-9-en-1-yl ((9Z,12Z)-octadeca-9,12-dien-1-yl) phosphonate	14.92	15.991	9.88	13.55	13.87	9.41
diOctadecyl phosphonate	15.56	17.379	10.11	14.2	15.2	9.7
Octadecyl undecyl phosphonate	12.13	14.212	9.55	10.76	12.01	8.4
(Z)-octadec-9-en-1-ol	7.50	7.975	7.71	7.5	6.91	5.76

We noticed that for all the constituents, ranges of values have been obtained. The gaps between these values are higher than more than 1 Log unit. All the results obtained are high (superior at 5).

Based on these observations, we decided to express Log Kow of each constituent as superior at the lower value obtained with the 4 QSARs used for the predictions. The lowest values have been obtained with MiLogP and MLOGP models.

The results are presented in the table below:

 

Chemical name (IUPAC)	Lowest value of Log Kow
di((Z)-octadec-9-en-1-yl) phosphonate	9.5
(Z)-octadec-9-en-1-yl octadecyl phosphonate	9.6
Methyl ((9Z,12Z)-octadeca-9,12-dien-1-yl) phosphonate	5.19
Methyl hexadecyl phosphonate	5.71
(Z)-methyl octadec-9-en-1-yl phosphonate	6.19
Methyl octadecyl phosphonate	5.85
(Z)-octadec-9-en-1-yl ((9Z,12Z)-octadeca-9,12-dien-1-yl) phosphonate	9.41
diOctadecyl phosphonate	9.7
Octadecyl undecyl phosphonate	8.4
(Z)-octadec-9-en-1-ol	5.76

 

 

 

Conclusions:

The test item possess a log Kow higher than 5.19.
The test item is considered to possess a potential for bioaccumulation

Executive summary:

Due to the test item nature (UVCB), QSAR estimation for the partition coefficient were done according to "Guidance on information requirements and chemical safety assessment Chapter R.6: QSARs and grouping of chemicals".

Indeed, experimental determination of this endpoint is considered to not be technically feasible. The recognised guidelines are relevant for pure substances or for multi consituents substances for which all the compounds can be quantified by an analytical method.

Four Qsar and six models were used for the estimation of Log Kow for each consituents of the test item. The results obtained were used in a weight of evidence approach to estimate the lowest value of test item Log Kow.

The test item possess a log Kow higher than 5.19.

The test item is considered to possess a potential for bioaccumulation

Description of key information

The log Kow was determined by Qsar in a weight of evidence approach based on four programs and six models.

Key value for chemical safety assessment

Log Kow (Log Pow):

5.19

at the temperature of:

20 °C

Additional information

Recognised Qsars were used to estimate the partition coefficient of the test item.

The validity of all the programs used cannot be demonstrated for each constituents of the test item. So the results obtained are used in a weight of evidence approach to estimate the log of the partition coefficient.

In order to use a protective approach, only the lowest Log Kow value of each constituent is estimated. Indeed, the uncertainties of the predictions are due to the high values obtained which are not included in the validity set of the models used.

The values obtained for each constituent of the test item are higher than 5.19. So the test item is considered to possess a potential for bioaccumulation.