tris(2-octyldodecyl) citrate

Adsorption / desorption

Administrative data

Endpoint:

adsorption / desorption: screening

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

21 April 2018

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
EPISUITE

2. MODEL (incl. version number)
KOCWIN v2.00 (September 2010)

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
SMILES: CCCCCCCCCCC(CCCCCCCC)COC(=O)CC(O)(CC(=O)OCC(CCCCCCCC)CCCCCCCCCC)C(=O) OCC(CCCCCCCC)CCCCCCCCCC
NAME: tris(2-octyldodecyl) citrate

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Estimated Koc (l/kg)
- Unambiguous algorithm:
 The same methodology as described in (Meylan et al, 1992) was used to develop the QSAR equations utilizing Molecular Connectivity Index (MCI).  Two separate regressions were performed.  The first regression related log Koc of non-polar compounds to the first-order MCI.  As noted above, non-polar compounds are now designated as "compounds having no correction factors" which simply means the MCI descriptor alone can adequately predict the Koc.  Measured log Koc values were fit to a simple linear equation of the form:

 log Koc  = a MCI  + b

where a and b are the coefficients fit by least-square analysis.  The 69 compounds used for this regression are listed in Appendix E.

The second regression included the 447 compounds having correction factors; these compounds are listed in Appendix F.  The correction factors descriptors are listed in Appendix D.  Correction factors are specific chemical classes or structural fragments.  The regression coefficients were derived via multiple linear regression of the correction descriptors to the residual error of the prediction from the non-polar equation.

Results Using Molecular Connectivity Index

The equation derived by the non-polar (no correction factor) regression is:

 log Koc  =  0.5213 MCI  +  0.60

    (n = 69, r2 = 0.967, std dev = 0.247, avg dev = 0.199)

for comparison, the previous version of PCKOCWIN used a very similar equation:

 log Koc  =  0.53 MCI  +  0.62

Adding in the correction factor regression yields the final MCI equation:

 log Koc  =  0.5213 MCI  +  0.60 + ΣPfN  

where ΣPfN is the summation of the products of all applicable correction factor coefficients from Appendix D multiplied by the number of times (N) that factor is counted for the structure.

The accuracy of the MCI estimation methodology is described in the Accuracy & Domain Section (Section 6.2).

See Appendix E, Appendix F and Appendix G for  lists of the chemicals used in the regressions and a supplemental validation list.

Estimation Using Log Kow

A traditional method of estimating soil adsorption Koc involves correlations developed with log octanol-water partition coefficient (log Kow) (Doucette, 2000).  Since an expanded experimental Koc database was available from the new MCI regression, it was decided to develop a log Kow estimation methodology that was potentially more accurate than existing log Kow QSARs for diverse structure datasets.

Effectively, the new log Kow methodology simply replaces the MCI descriptor with log Kow and derives similar equations.  The derivation uses the same training and validation data sets.  The training set is divided into the same non-polar (no correction factors) and correction factor sets.  The same correction factors are also used.

Separate equations correlating log Koc with log Kow were derived for nonpolar and polar compounds because it was statistically more accurate to do so than to use the approach taken with the MCI-based method.  The equation derived by the non-polar (no correction factor) regression is:

 log Koc  =  0.8679 Log Kow  -  0.0004

    (n = 68, r2 = 0.877, std dev = 0.478, avg dev = 0.371)

One non-polar compound was removed from the regression (hexabromobiphenyl) because it was the only compound without a recommended experimental log Kow and the accuracy of its estimated log Kow (9.10) is suspect.  This equation is used for any compound having no correction factors.

For the multiple-linear regression using correction factors, log Kow was included as an individual descriptor.  For compounds having correction factors, the equation is:

 log Koc  =  0.55313 Log Kow  +  0.9251 + ΣPfN  

where ΣPfN is the summation of the products of all applicable correction factor coefficients from Appendix D multiplied by the number of times (N) that factor is counted for the structure.

The accuracy of the log Kow estimation methodology is described in the Accuracy & Domain Section (Section 6.2).

See Appendix E, Appendix F and Appendix G for  lists of the chemicals used in the regressions and a supplemental validation list.

- Defined domain of applicability: See "Accuracy & Domain.pdf" appended below.


5. APPLICABILITY DOMAIN
See "Accuracy & Domain.pdf" appended below.

6. ADEQUACY OF THE RESULT
The QSAR model was used as the water solubility of the test substance is too low to allow for an experimental test. The model has been fully validated by a reputable government agency. The result is therefore considered adequatly reliable for use as the basis of the classification and labelling and PBT/vPvB assessment. The result is of the order of magnitude expected from subsatnces with high Log Pow and low water solubility characteristics.

Data source

Reference

Reference Type:

publication

Title:

EPI Suite V4.11 - KOCWIN

Year:

2010

Bibliographic source:

KOCWIN v2.00 - Meylan et al, 1992 & SRC, 1991

Materials and methods

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

The QSAR model was used as the water solubility of the test substance fell below the limit of quantification in an experimental test. The model has been fully validated by a reputable government agency. The result is therefore considered adequatly reliable for use as the basis of the classification and labelling and PBT/vPvB assessment.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,2,3-tris(2-octyldodecyl) 2-hydroxypropane-1,2,3-tricarboxylate

EC Number:

603-121-2

Cas Number:

126121-35-5

Molecular formula:

C66H128O7

IUPAC Name:

1,2,3-tris(2-octyldodecyl) 2-hydroxypropane-1,2,3-tricarboxylate

Test material form:

liquid

Details on test material:

Tris(octyldodecyl) citrate 99.87 %
Bis(octyldodecyl) citrate 0.13 %

Results and discussion

Adsorption coefficient

Adsorption coefficient 1

Sample No.:

#1

Type:

Koc

Value:

10 000 000 000 L/kg

Remarks on result:

other: QSAR: Koc estimate from MCI

Adsorption coefficient 2

Sample No.:

#1

Type:

log Koc

Value:

15.291 dimensionless

Remarks on result:

other: QSAR: Log Koc estimate from MCI

Adsorption coefficient 3

Sample No.:

#2

Type:

Koc

Value:

1 295 000 000 000 000 L/kg

Remarks on result:

other: QSAR: Koc estimated from Log Kow

Adsorption coefficient 4

Sample No.:

#2

Type:

log Koc

Value:

15.112 dimensionless

Remarks on result:

other: QSAR: Log Koc estimated from Log Pow

Any other information on results incl. tables

Koc Estimate from MCI:

First Order Molecular Connectivity Index	35.686
Non-Corrected Log Koc (0.5213 MCI + 0.60)	19.2029
Fragment Correction(s):
1 Aliphatic Alcohol (-C-OH)	-1.3179
2 Ester (-C-CO-O-C-) or (HCO-O-C)	-2.5939
Corrected Log Koc	15.2911
Estimated Koc	1E+10 L/kg

Koc Estimate from Log Kow:

Log Kow (Kowwin estimate)	26.63
Non-Corrected Log Koc (0.55313 logKow + 0.9251)	15.6550
Fragment Correction(s):
1 Aliphatic Alcohol (-C-OH)	-0.4114
2Ester (-C-CO-O-C-) or (HCO-O-C)	-0.1312
Corrected Log Koc	15.1123
Estimated Koc	1.295E+15 L/kg

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

The test material was determined to have a Log Koc of 15.2911 based on MCI and 15.1123 based on Log Kow.

Executive summary:

In this validated QSAR (KOCWIN) study, the Log Koc of the test material was determined to be 15.2911 based on MCI and 15.1123 based on Log Kow