Dipentaerythritol hexaesters of 3,5,5-trimethylhexanoic and n-heptanoic acids

Adsorption / desorption

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

adsorption / desorption, other

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

December 2018

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
Program KOCWIN included in EPISUITE (Estimation Programs Interface Suite™ for Microsoft® Windows, v 4.11)

2. MODEL (incl. version number)
KOCWIN™ program estimates the organic carbon-normalized sorption coefficient for soil and sediment; i.e. KOC.
KOC is estimated using two different models: the Sabljic molecular connectivity method using the Molecular Connectivity Index (MCI) with improved correction factors; and the traditional method based on log KOW to which fragment corrections are also applied.
The results summarized in this endpoint correspond to the first model.
Koc is calculated using the following formula: Koc = Kd / %OC X 100 and expressed as Liters per
Kilogram of soil. Kd (partitioning between the solid-phase (soil or sediment) and solution-phase (water) at equilibrium) is normalized by multiplying the percent organic carbon content of the soil by 100.

This QSAR estimation methodology is described completely in a journal article (Meylan et al, 1992) and in a report prepared for the EPA (SRC, 1991).
Reference: Meylan, W., P.H. Howard and R.S. Boethling, "Molecular Topology/Fragment Contribution Method for Predicting Soil Sorption Coefficients", Environ. Sci. Technol. 26: 1560-7 (1992).

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
DPE777777 (constituent #1):
O=C(CCCCCC)OCC(COC(=O)CCCCCC)(COC(=O)CCCCCC)COCC(COC(=O)CCCCCC)(COC(=O)CCCCCC)COC(=O)CCCCCC

DPE777779 (constituent #2):
O=C(CCCCCC)OCC(COC(=O)CCCCCC)(COC(=O)CC(C)CC(C)(C)C)COCC(COC(=O)CCCCCC)(COC(=O)CCCCCC)COC(=O)CCCCCC

DPE777799 (constituent #3):
O=C(CCCCCC)OCC(COC(=O)CCCCCC)(COC(=O)CC(C)CC(C)(C)C)COCC(COC(=O)CCCCCC)(COC(=O)CC(C)CC(C)(C)C)COC(=O)CCCCCC

DPE777999 (constituen #4):
O=C(CCCCCC)OCC(COC(=O)CC(C)CC(C)(C)C)(COC(=O)CC(C)CC(C)(C)C)COCC(COC(=O)CCCCCC)(COC(=O)CC(C)CC(C)(C)C)COC(=O)CCCCCC

DPE779999 (constituent #5):
O=C(CCCCCC)OCC(COC(=O)CC(C)CC(C)(C)C)(COC(=O)CC(C)CC(C)(C)C)COCC(COC(=O)CC(C)CC(C)(C)C)(COC(=O)CC(C)CC(C)(C)C)COC(=O)CCCCCC

DPE799999 (constituent #6):
O=C(CCCCCC)OCC(COC(=O)CC(C)CC(C)(C)C)(COC(=O)CC(C)CC(C)(C)C)COCC(COC(=O)CC(C)CC(C)(C)C)(COC(=O)CC(C)CC(C)(C)C)COC(=O)CC(C)CC(C)(C)C

DPE999999 (constituent #7):
O=C(CC(C)CC(C)(C)C)OCC(COC(=O)CC(C)CC(C)(C)C)(COC(=O)CC(C)CC(C)(C)C)COCC(COC(=O)CC(C)CC(C)(C)C)(COC(=O)CC(C)CC(C)(C)C)COC(=O)CC(C)CC(C)(C)(C)

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
[Explain how the model fulfils the OECD principles for (Q)SAR model validation. Consider attaching the QMRF or providing a link]

1. Defined endpoint: log Koc – soil adsorption coefficient of organic compounds.

2. Unambiguous algorithm:
log Koc = 0.5213 MCI + 0.60 + ΣPfN
MCI – molecular connectivity index, ΣPfN - summation of the products of all applicable correction factor coefficients available in the data set multiplied by the number of times (N) that factor is counted for the structure.

3. Applicability domain: Currently, there is no universally accepted definition of model domain. The training set of the model contains diverse molecules, so that the fragment library is abundant. It is however possible that a compound has functional groups or other structural features that are not represented in the training set and for which no fragment coefficients were developed. Additionally, there can be more instances of a given fragment than the maximum for all training set compounds. These points should be taken into consideration while interpreting test results.
Molecular weight limits of the training set: 32-665 g/mol
Log Kow limits: -2.11-9.10
4. Appropriate measures of goodness of fit, robustness and predictivity: for the statistics, training data set has been split up into two subsets: the one containing non-polar substances with no fragments subjected to corrections (i.e. those with ΣPfN = 0) and the one containing the remaining ones. For the non-polar set: N = 69 compounds, correlation coefficient R2= 0.967, standard deviation sd = 0.247 and average deviation ad = 0.199. For the second set: N = 447 compounds, correlation coefficient R2= 0.9, standard deviation sd = 0.34 and average deviation ad = 0.273. For the external validation data set: N = 158 compounds, correlation coefficient R2= 0.85, standard deviation sd = 0.583 and average deviation ad = 0.459. For the 516 compounds in the training set, 93% are within 0.6 log units and 100% within 1 log unit.

5. Mechanistic interpretation if possible: The methodology and relationship between the first order molecular connectivity index (MCI) and adsorption coefficient is outlined in the reference paper: Meylan, W., P.H. Howard and R.S. Boethling, "Molecular Topology/Fragment Contribution Method for Predicting Soil Sorption Coefficients", Environ. Sci. Technol. 26: 1560-7 (1992). MCI was initially successfully used to predict soil sorption coefficients for non-polar organics, and the developed new estimation method based on MCI and series of statistically derived fragment contribution factors made it useful also for the polar ones.

5. APPLICABILITY DOMAIN
[Explain how the substance falls within the applicability domain of the model]
These models have no universally accepted definition of model domain, but since the substance is outside the molecular weight and Kow range of the training set, the results should be taken with caution.
The functional groups present in the constituents of the substance (ester groups) are included in the model's dataset. Each constituent has the following generic structure: R1-C(=O)-O-R2
R1 = n-hexyl for the n-heptanoic esters. n-Hexyl fragment is included in the fragment library and therefore its contribution to the calculated log Koc is accurate within the model.
R1 = 3,5,5-trimethyloctyl for the 3,5,5-trimethylhexyl esters. This fragment is not included in the fragment library and iso-Butyl fragment is used instead. The substitute is a shorter carbon chain with less branching.
R2 = DPE pentaester. This fragment is not included in the fragment library and -CH2-(t-Bu) fragment is used instead, which contains the same structure than the DPE actual fragment up to the 3 closet carbon atoms.

6. ADEQUACY OF THE RESULT
Although the definite calculated values (log Koc > 13 for all constituents) may not be fully reliable, they indicate a high adsorption potential, as can be expected from the high log Kow and low solubility in water of the substance.
Taken into account the limitations in the applicability domain discussed above, a value of log Koc > 5 is adopted for Dipentaerythritol hexaesters with n-heptanoic and 3,5,5-trimethylhexanoic acids. This value is considered adequate for assessment of the adsorption / desorption potential of the substance and reflects that very strong sorption to soil / sediment and negligible migration to ground water are expected.

Reason / purpose for cross-reference:

other: QPRF reports

GLP compliance:

no

Type of method:

other: calculation

Media:

soil

Sample No.:

#1

Type:

log Koc

Value:

13.52 dimensionless

Temp.:

25 °C

Sample No.:

#1

Type:

Koc

Value:

10 000 000 000 L/kg

Temp.:

25 °C

Sample No.:

#2

Type:

log Koc

Value:

13.8 dimensionless

Temp.:

25 °C

Sample No.:

#2

Type:

Koc

Value:

10 000 000 000 L/kg

Temp.:

25 °C

Sample No.:

#3

Type:

log Koc

Value:

14.08 dimensionless

Temp.:

25 °C

Sample No.:

#3

Type:

Koc

Value:

10 000 000 000 L/kg

Temp.:

25 °C

Sample No.:

#4

Type:

log Koc

Value:

14.37 dimensionless

Temp.:

25 °C

Sample No.:

#4

Type:

Koc

Value:

10 000 000 000 L/kg

Temp.:

25 °C

Sample No.:

#5

Type:

log Koc

Value:

14.65 dimensionless

Temp.:

25 °C

Sample No.:

#5

Type:

Koc

Value:

10 000 000 000 L/kg

Temp.:

25 °C

Sample No.:

#6

Type:

log Koc

Value:

14.93 dimensionless

Temp.:

25 °C

Sample No.:

#6

Type:

Koc

Value:

10 000 000 000 L/kg

Temp.:

25 °C

Sample No.:

#7

Type:

log Koc

Value:

15.21 dimensionless

Temp.:

25 °C

Sample No.:

#7

Type:

Koc

Value:

10 000 000 000 L/kg

Temp.:

25 °C

Validity criteria fulfilled:

yes

Conclusions:

Although the definite calculated values (log Koc > 13 for all constituents) may not be fully reliable due to the high molecular weight of the constituents of the substance, they indicate a high adsorption potential, as can be expected from the high log Kow and low solubility in water of the substance.
Taken into account the limitations in the applicability domain discussed above, a value of log Koc > 5 is adopted for Dipentaerythritol hexaesters with n-heptanoic and 3,5,5-trimethylhexanoic acids. This value is considered adequate as supporting information for the assessment of the adsorption / desorption potential of the substance and reflects that very strong sorption to soil / sediment and negligible migration to ground water are expected.

Reference 2

Endpoint:

adsorption / desorption, other

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

December 2018

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
Program KOCWIN included in EPISUITE (Estimation Programs Interface Suite™ for Microsoft® Windows, v 4.11)

2. MODEL (incl. version number)
KOCWIN™ program estimates the organic carbon-normalized sorption coefficient for soil and sediment; i.e. KOC.
KOC is estimated using two different models: the Sabljic molecular connectivity method using the Molecular Connectivity Index (MCI) with improved correction factors; and the traditional method based on log KOW to which fragment corrections are also applied.
The results summarized in this endpoint correspond to the second model, the log Kow method for nonpolar and polar organics.
The method involves correlations developed with log octanol-water partition coefficients. Separate equations correlating log Koc with log Kow were derived for non-polar and polar compounds because it was statistically more accurate.
Koc is calculated using the following formula: Koc = Kd / %OC X 100 and expressed as Liters per
Kilogram of soil. Kd (partitioning between the solid-phase (soil or sediment) and solution-phase (water) at equilibrium) is normalized by multiplying the percent organic carbon content of the soil by 100.

This QSAR estimation methodology is described completely in a journal article (Meylan et al, 1992) and in a report prepared for the EPA (SRC, 1991).
Reference: Meylan, W., P.H. Howard and R.S. Boethling, "Molecular Topology/Fragment Contribution Method for Predicting Soil Sorption Coefficients", Environ. Sci. Technol. 26: 1560-7 (1992).

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
DPE777777 (constituent #1): O=C(CCCCCC)OCC(COC(=O)CCCCCC)(COC(=O)CCCCCC)COCC(COC(=O)CCCCCC)(COC(=O)CCCCCC)COC(=O)CCCCCC

DPE777779 (constituent #2):
O=C(CCCCCC)OCC(COC(=O)CCCCCC)(COC(=O)CC(C)CC(C)(C)C)COCC(COC(=O)CCCCCC)(COC(=O)CCCCCC)COC(=O)CCCCCC

DPE777799 (constituent #3):
O=C(CCCCCC)OCC(COC(=O)CCCCCC)(COC(=O)CC(C)CC(C)(C)C)COCC(COC(=O)CCCCCC)(COC(=O)CC(C)CC(C)(C)C)COC(=O)CCCCCC

DPE777999 (constituen #4):
O=C(CCCCCC)OCC(COC(=O)CC(C)CC(C)(C)C)(COC(=O)CC(C)CC(C)(C)C)COCC(COC(=O)CCCCCC)(COC(=O)CC(C)CC(C)(C)C)COC(=O)CCCCCC

DPE779999 (constituent #5):
O=C(CCCCCC)OCC(COC(=O)CC(C)CC(C)(C)C)(COC(=O)CC(C)CC(C)(C)C)COCC(COC(=O)CC(C)CC(C)(C)C)(COC(=O)CC(C)CC(C)(C)C)COC(=O)CCCCCC

DPE799999 (constituent #6):
O=C(CCCCCC)OCC(COC(=O)CC(C)CC(C)(C)C)(COC(=O)CC(C)CC(C)(C)C)COCC(COC(=O)CC(C)CC(C)(C)C)(COC(=O)CC(C)CC(C)(C)C)COC(=O)CC(C)CC(C)(C)(C)

DPE999999 (constituent #7):
O=C(CC(C)CC(C)(C)C)OCC(COC(=O)CC(C)CC(C)(C)C)(COC(=O)CC(C)CC(C)(C)C)COCC(COC(=O)CC(C)CC(C)(C)C)(COC(=O)CC(C)CC(C)(C)C)COC(=O)CC(C)CC(C)(C)

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
[Explain how the model fulfils the OECD principles for (Q)SAR model validation. Consider attaching the QMRF or providing a link]
1. Defined endpoint: log Koc – soil adsorption coefficient of organic compounds.
2. Unambiguous algorithm:
log Koc = 0.8679 log Kow – 0.0004 for non-polar compounds with no correction factor.
Log Koc = 0.55313 log Kow + 0.9251 +ΣPfN
ΣPfN - summation of the products of all applicable correction factor coefficients available in the data set multiplied by the number of times (N) that factor is counted for the structure.
3. Applicability domain: currently, there is no universally accepted definition of model domain. It is possible that a compound has functional groups or other structural features that are not represented in the training set and for which no correction factors were calculated. Additionally, there can be more instances of a given fragment than the maximum for all training set compounds. These points should be taken into consideration while interpreting test results.
Molecular weight limits of the training set: 32-665 g/mol
Log Kow limits: -2.11-8.12.
4. Appropriate measures of goodness of fit, robustness and predictivity: for the statistics, training data set has been split up into two subsets: the one containing non-polar substances with no fragments subjected to corrections (i.e. those withΣPfN = 0) and the one containing the remaining ones. For the non-polar set:N = 68 compounds, correlation coefficient R2= 0.877, standard deviation sd = 0.478 and average deviation ad = 0.371. For the second set: N = 447 compounds, correlation coefficient R2= 0.855, standard deviation sd = 0.396 and average deviation ad = 0.037. For the external validation data set: N = 150 compounds, correlation coefficient R2= 0.778, standard deviation sd = 0.679 and average deviation ad = 0.494.
5. Mechanistic interpretation if possible: The methodology and relationship between the first order molecular connectivity index (MCI) and adsorption coefficient is outlined in the reference paper: Meylan, W., P.H. Howard and R.S. Boethling, "Molecular Topology/Fragment Contribution Method for Predicting Soil Sorption Coefficients", Environ. Sci. Technol. 26: 1560-7 (1992). MCI was initially successfully used to predict soil sorption coefficients for non-polar organics, and the developed new estimation method based on MCI and series of statistically derived fragment contribution factors made it useful also for the polar ones.


5. APPLICABILITY DOMAIN
[Explain how the substance falls within the applicability domain of the model]
These models have no universally accepted definition of model domain, but since the substance is outside the molecular weight and Kow range of the training set, the results should be taken with caution.
Koc is calculated from log Kow and then some fragment corrections are applied:
1- Eher , alphatic (-C-O-C-) for the ether group in DPE
2- Ester (-C-CO-O-C-), for the ester groups between DPE and the fatty acids

The functional groups present in the constituents of the substance are included in the model's correction factors.

6. ADEQUACY OF THE RESULT
Although the definite calculated values (log Koc > 9 for all constituents) may not be fully reliable, they indicate a high adsorption potential, as can be expected from the high log Kow and low solubility in water of the substance.
Taken into account the limitations in the applicability domain discussed above, a value of log Koc > 5 is adopted for Dipentaerythritol hexaesters with n-heptanoic and 3,5,5-trimethylhexanoic acids. This value is considered adequate for assessment of the adsorption / desorption potential of the substance and reflects that very strong sorption to soil / sediment and negligible migration to ground water are expected.

Reason / purpose for cross-reference:

(Q)SAR model reporting (QMRF)

Reason / purpose for cross-reference:

other: QPRF reports

GLP compliance:

no

Type of method:

other: calculation

Media:

soil

Sample No.:

#1

Type:

log Koc

Value:

9.42 dimensionless

Temp.:

25 °C

Sample No.:

#1

Type:

Koc

Value:

2 600 000 000 L/kg

Temp.:

25 °C

Sample No.:

#2

Type:

log Koc

Value:

9.87 dimensionless

Temp.:

25 °C

Sample No.:

#2

Type:

Koc

Value:

7 200 000 000 L/kg

Temp.:

25 °C

Sample No.:

#3

Type:

log Koc

Value:

10.3 dimensionless

Temp.:

25 °C

Sample No.:

#3

Type:

Koc

Value:

20 000 000 000 L/kg

Temp.:

25 °C

Sample No.:

#4

Type:

log Koc

Value:

10.73 dimensionless

Temp.:

25 °C

Sample No.:

#4

Type:

Koc

Value:

55 000 000 000 L/kg

Temp.:

25 °C

Sample No.:

#5

Type:

log Koc

Value:

11.18 dimensionless

Temp.:

25 °C

Sample No.:

#5

Type:

Koc

Value:

150 000 000 000 L/kg

Temp.:

25 °C

Sample No.:

#6

Type:

log Koc

Value:

11.62 dimensionless

Temp.:

25 °C

Sample No.:

#6

Type:

Koc

Value:

419 000 000 000 L/kg

Temp.:

25 °C

Sample No.:

#7

Type:

log Koc

Value:

12.06 dimensionless

Temp.:

25 °C

Sample No.:

#7

Type:

Koc

Value:

1 160 000 000 000 L/kg

Temp.:

25 °C

Validity criteria fulfilled:

yes

Conclusions:

Although the definite calculated values (log Koc > 9 for all constituents) may not be fully reliable due to the high molecular weight of the constituents of the substance, they indicate a high adsorption potential, as can be expected from the high log Kow and low solubility in water of the substance.
Taken into account the limitations in the applicability domain discussed above, a value of log Koc > 5 is adopted for Dipentaerythritol hexaesters with n-heptanoic and 3,5,5-trimethylhexanoic acids. This value is considered adequate as supporting information for the assessment of the adsorption / desorption potential of the substance and reflects that very strong sorption to soil / sediment and negligible migration to ground water are expected.

Reference 3

Endpoint:

adsorption / desorption: screening

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

In accordance to Regulation (EC) No 1907/2006 Annex XI, 1.5 a read across from the structurally similar analogue substance Dipentaerythritol with fatty acids, C5 and C9iso was conducted to fulfil the data requirements according to Annex VIII of Dipentaerythritol hexaesters of 3,5,5-trimethylhexanoic and n-heptanoic acids (CAS 1379424-11-9) in regards to Adsorption/desorptin screening.

This read-across is justified in detail in the overall summary (IUCLID section 5) and within the analogue justification in IUCLID section 13. Both substances have got the same alcohol component (dipentaerythritol) and similar fatty acid chain lengths (C7 and C9iso for the target substance compared to C5 and C9iso for the source substance).
An study following OECD Guideline 121 (Estimation of the Adsorption Coefficient (Koc) on Soil and on Sewage Sludge using High Performance Liquid Chromatography (HPLC)) under GLP conditions was performed for the source substance. The estimated Koc value was 5.63.

Based on the result from the structurally related source substance, the Koc of the target substance Dipentaerythritol hexaesters of 3,5,5-trimethylhexanoic and n-heptanoic acids (CAS 1379424-11-9) is estimated to be 5.63.

Reason / purpose for cross-reference:

read-across source

Key result

Type:

log Koc

Value:

5.63 dimensionless

Validity criteria fulfilled:

yes

Conclusions:

Adsoption/ desorption screening test (HPLC) estimates a log Koc value of 5.63.

Executive summary:

An available adsoption/desorption screening test with the subsance EC number 444-000-2 estimates a Koc value of 5.63.

Based on the result from the structurally related substance, characterized by a similar ecotoxicological profile and in accordance to Regulation (EC) No 1907/2006 Annex XI, 1.5 (read-across from a surrogate), it can be concluded that for substance Dipentaerythritol hexaesters of 3,5,5-trimethylhexanoic and n-heptanoic, the estimated Koc value is 5.63.

Reference 4

Endpoint:

adsorption / desorption: screening

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 121 (Estimation of the Adsorption Coefficient (Koc) on Soil and on Sewage Sludge using High Performance Liquid Chromatography (HPLC))

Version / remarks:

OECD draft 1997

GLP compliance:

yes

Type of method:

HPLC estimation method

Media:

soil

Key result

Type:

log Koc

Value:

5.63 dimensionless

Validity criteria fulfilled:

yes

Conclusions:

log Koc > 5.63

Executive summary:

Adsorption / desorption coefficient on soil was estimating using HPLC in a GLP study according to draft guideline OECD 121 (1997). The test could not determine the exact value of Koc, but a lower threshold value of log Koc > 5.63.

Description of key information

log Koc > 5.63

Read-across from analogue substance Dipentaerythritol with fatty acids, C5 and C9iso (EC 444 -000 -2) was conducted. This read across is justified in detail in IUCLID section 13.

The adsorption/desorption potential of the read across substance was analysed in a HPLC screening study according to GLP and "OECD draft document (1997): Estimation of the Adsorption Coefficient (Koc) on Soil and on Sewage Sludge using HPLC" (Lumsden, 2000). The test substance was analysed for its elution behaviour by comparison with 11 reference substances using HPLC method. The retention time of the test substance exceeded the range of the calibration curve and therefore, the log Koc is not given as distinct value but stated to be > 5.63 (highest log Koc among reference substances).

Additionally, the QSAR model KOCWIN v2.0 based on molecular connectivity index (MCI) was used to predict log Koc for Dipentaerythritol hexaesters of 3,5,5 -trimethylhexanoic and n-heptanoic acids. The log Koc was calculated to be >13 supporting the result form the RA, showing the substance has a high adsorption potential to organic particles in soil and sediment.