Esterification products of Guerbet alcohols, C24-26, branched and cyclic with benzene-1,2,4-tricarboxylic acid 1,2-anhydride (3:1)

Adsorption / desorption

Link to relevant study record(s)

Reference

Endpoint:

adsorption / desorption: screening

Type of information:

(Q)SAR

Adequacy of study:

key study

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 (v4.11)

2. MODEL (incl. version number)
KOCWIN v2.01

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
SMILES 1: CCCCCCCCCCCCC(CCCCCCCCCC)COC(=O)c1ccc(c(c1)C(=O)OCC(CCCCCCCCCC)CCCCCCCCCCCC)C(=O)OCC(CCCCCCCCCC)CCCCCCCCCCCC [C24 Guerbet alcohols based]
SMILES 2: CCCC(C)CCCCC(C)CC(CCCC(C)CCCCC)COC(=O)c1ccc(c(c1)C(=O)OCC(CCC(C)CCCCCC)CCCCC(C)CCCCCC)C(=O)OCC(CCCC(C)CCCCC)CCC(C)CCCCC(C)CC [branched C24 Guerbet alcohols based]
SMILES 3: C1CCCCC1CCCCC(CCCCCCC1CCCCC1)COC(=O)c1cc(c(cc1)C(=O)OCC(CCCCCCC1CCCCC1)CCCC1CCCCCC1)C(=O)OCC(CCCCCCC1CCCCC1)CCCC1CCCCCC1 [cyclic C24 Guerbet alcohols based]
SMILES 4: CCCCCCCCCCCCCC(CCCCCCCCCCC)COC(=O)c1ccc(c(c1)C(=O)OCC(CCCCCCCCCCC)CCCCCCCCCCCCC)C(=O)OCC(CCCCCCCCCCC)CCCCCCCCCCCCC [C26 Guerbet alcohols based]
SMILES 5: CCCCCC(C)CCCC(C)CC(CCCC(C)CCCCCC)COC(=O)c1ccc(c(c1)C(=O)OCC(CCCC(C)CCCCCC)CCC(C)CCCCC(C)CCC)C(=O)OCC(CCCC(C)CCCCCC)CC(C)CCCCCC(C)CCC [branched C26 Guerbet alcohols based]
SMILES 6: C1CCCCC1CCCCCC(CCCCCCCC1CCCCC1)COC(=O)c1cc(c(cc1)C(=O)OCC(CCCCCCCC1CCCCC1)CCCCC1CCCCCC1)C(=O)OCC(CCCCCCCC1CCCCC1)CCCCCC1CCCCC1 [cyclic C26 Guerbet alcohols based]

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
A reliable QSAR model was used to calculate the adsorption/desorption potential of Esterification products of Guerbet alcohols, C24-26, branched and cyclic with benzene-1,2,4-tricarboxylic acid 1,2-anhydride by using representative structures covering the lower and the upper MW range. Koc values were calculated using the KOCWIN v2.01 module embedded within the EPISuite (v4.11) computer model.
EPISuite and its modules (including KOCWIN) have been utilized by the scientific community for prediction of phys/chem properties and environmental fate and effect properties since the 1990’s. The program underwent a comprehensive review by a panel of the US EPA’s independent Science Advisory Board (SAB) in 2007. The SAB summarized that the EPA used sound science to develop and refine EPISuite. The SAB also stated that the property estimation routines (PERs) satisfy the Organization for Economic Cooperation and Development (OECD) principles established for quantitative structure-activity relationship ((Q)SAR) validation.
The EPISuite modules (including KOCWIN) have been incorporated into the OECD Toolbox. Inclusion in the OECD toolbox requires specific documentation, validation and acceptability criteria and subjects EPISuite to international use, review, providing a means for receiving additional and on-going input for improvements.
In summary, the EPISuite modules (including KOCWIN) have had their scientific validity established repeatedly.
- Defined endpoint and unambiguous algorithm:
KOCWIN estimates Koc with two separate estimation methodologies: (1) estimation using first-order Molecular Connectivity Index (MCI) and (2) estimation using log Kow (octanol-water partition coefficient).
The initial KOCWIN (version 1) model estimated Koc solely with a QSAR utilizing Molecular Connectivity Index (MCI). This QSAR estimation methodology is described completely in a journal article (Meylan et al, 1992) and in a report prepared for the US EPA (SRC, 1991). KOCWIN (version 2) utilizes the same methodology, but the QSAR has been re-regressed using a larger database of experimental Koc values that includes many new chemicals and structure types. Two separate regressions were performed. The first regression related log Koc of non-polar compounds to the first-order MCI.
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.
- Defined domain of applicability:
According to the KOCWIN documentation, there is currently no universally accepted definition of model domain. However, the documentation does provide information for reliability of the calculations. Estimates will possibly be less accurate for compounds that 1) have a MW outside the range of the training set compounds and 2) have a functional group(s) or other structural features not represented in the training set, and for which no fragment coefficient was developed; and that a compound has none of the fragments in the model’s fragment library.
- Appropriate measures of goodness-of-fit and robustness and predictivity:
KOCWIN calculated the Koc values based on the following equations:
Estimation Using MCI: log Koc = 0.5213 MCI + 0.60
Estimation Using Log Kow: log Koc = 0.8679 Log Kow - 0.0004
The KOCWIN model had the following statistics:
MCI Methodology (Training Set): number = 69 correlation coef (r2) = 0.967
MCI Methodology (Validation Set): number = 158 correlation coef (r2) = 0.850
log Kow Methodology (Training Set): number = 68 correlation coef (r2) = 0.877
log Kow Methodology (Validation Set): number = 150 correlation coef (r2) = 0.778
These correlation coefficients indicate the KOCWIN model calculates results that are equivalent to those generated experimentally and are, hence, adequate for the purpose of classification and labelling and/or risk assessment.
Overall, the MCI methodology is somewhat considered more accurate than the Log Kow methodology, although both methods yield good results. If the Training datasets are combined in to one dataset of 516 compounds (69 having no corrections plus 447 with corrections), the MCI methodology has an r2, standard deviation and average deviation of 0.916, 0.330 and 0.263, respectively, versus 0.86, 0.429 and 0.321 for the Log Kow methodology.

5. APPLICABILITY DOMAIN
As described above, according to the KOCWIN documentation, there is currently no universally accepted definition of model domain. In general, the intended application domain for all models embedded in EPISuite is organic chemicals. Specific compound classes, besides organic chemicals, require additional correction factors. Indicators for the general applicability of the KOCWIN model are the molecular weight of the target substance and the identification of functional group(s) or other structural features and their representation in the training set. The training set molecular weights are within the range of 32.04 – 665.02 with an average molecular weight of 224.4 (Validation set molecular weights: 73.14 – 504.12 and average of 277.8).

--------------------------- KOCWIN v2.01 Results ---------------------------
SMILES (1): CCCCCCCCCCCCC(CCCCCCCCCC)COC(=O)c1ccc(c(c1)C(=O)OCC(CCCCCCCCCC)CCCCCCCCCCCC)C(=O)OCC(CCCCCCCCCC)CCCCCCCCCCCC [C24 Guerbet alcohols based]
SMILES (2): CCCC(C)CCCCC(C)CC(CCCC(C)CCCCC)COC(=O)c1ccc(c(c1)C(=O)OCC(CCC(C)CCCCCC)CCCCC(C)CCCCCC)C(=O)OCC(CCCC(C)CCCCC)CCC(C)CCCCC(C)CC [branched C24 Guerbet alcohols based]
SMILES (3): C1CCCCC1CCCCC(CCCCCCC1CCCCC1)COC(=O)c1cc(c(cc1)C(=O)OCC(CCCCCCC1CCCCC1)CCCC1CCCCCC1)C(=O)OCC(CCCCCCC1CCCCC1)CCCC1CCCCCC1 [cyclic C24 Guerbet alcohols based]

MOL FOR: C81 H150 O6 (C81 H138 O6 cyclic)
MOL WT : 1220.10 (1208.00 cyclic)
(1) Koc Estimate from MCI:
First Order Molecular Connectivity Index: 42.840 (1)/ 41.991 (2)/ 42.946 (3)
Non-Corrected Log Koc (0.5213 MCI + 0.60): 22.9323 (1)/ 22.4896 (2)/ 22.9875 (3)
Fragment Correction(s):
2 Ester (-C-CO-O-C-) or (HCO-O-C): -2.5939
Corrected Log Koc: 20.3384 (1)/19.8957 (2)/ 20.3936 (3)
Estimated Koc: 1e+010 L/kg (SMILES 1 -3)
(2) Koc Estimate from Log Kow:
Log Kow (Kowwin estimate): 35.16 (1)/ 34.58 (2)/ 34.05 (3)
Non-Corrected Log Koc (0.55313 logKow + 0.9251): 20.3731 (1)/ 20.0523 (2)/ 19.7592 (3)
Fragment Correction(s):
2 Ester (-C-CO-O-C-) or (HCO-O-C): -0.1312
Corrected Log Koc: 20.2420 (1)/ 19.9211 (2)/ 19.6280 (3)
Estimated Koc: 1.746e+020 L/kg (1)/ 8.34e+019 L/kg (2)/ 4.246e+019 L/kg (3)

--------------------------- KOCWIN v2.01 Results ---------------------------
SMILES (4): CCCCCCCCCCCCCC(CCCCCCCCCCC)COC(=O)c1ccc(c(c1)C(=O)OCC(CCCCCCCCCCC)CCCCCCCCCCCCC)C(=O)OCC(CCCCCCCCCCC)CCCCCCCCCCCCC [C26 Guerbet alcohols based]
SMILES (5): CCCCCC(C)CCCC(C)CC(CCCC(C)CCCCCC)COC(=O)c1ccc(c(c1)C(=O)OCC(CCCC(C)CCCCCC)CCC(C)CCCCC(C)CCC)C(=O)OCC(CCCC(C)CCCCCC)CC(C)CCCCCC(C)CCC [branched C26 Guerbet alcohols based]
SMILES (6): C1CCCCC1CCCCCC(CCCCCCCC1CCCCC1)COC(=O)c1cc(c(cc1)C(=O)OCC(CCCCCCCC1CCCCC1)CCCCC1CCCCCC1)C(=O)OCC(CCCCCCCC1CCCCC1)CCCCCC1CCCCC1 [cyclic C26 Guerbet alcohols based]

MOL FOR: C87 H162 O6 (C87 H150 O6 cyclic)
MOL WT: 1304.26 (1292.16 cyclic)
(1) Koc Estimate from MCI:
First Order Molecular Connectivity Index: 45.840 (4)/ 44.885 (5)/ 45.946 (6)
Non-Corrected Log Koc (0.5213 MCI + 0.60): 24.4962 (4)/ 23.9982 (5)/ 24.5514 (6)
Fragment Correction(s):
2 Ester (-C-CO-O-C-) or (HCO-O-C): -2.5939
Corrected Log Koc: 21.9023 (4)/ 21.4042 (5)/ 21.9575 (6)
Estimated Koc: 1e+010 L/kg (SMILES 4-6)
(2) Koc Estimate from Log Kow:
Log Kow (Kowwin estimate): 38.11 (4)/ 37.45 (5)/ 37.00 (6)
Non-Corrected Log Koc (0.55313 logKow + 0.9251): 22.0049 (4)/ 21.6398 (5)/ 21.3909 (6)
Fragment Correction(s):
2 Ester (-C-CO-O-C-) or (HCO-O-C): -0.1312
Corrected Log Koc: 22.6868 (4)/ 21.5086 (5)/ 21.2597 (6)
Estimated Koc: 7.476e+021 L/kg (4)/ 3.226e+021 L/kg (5)/ 1.819e+021 L/kg (6)

The selected structures represent the lower and the upper MW range, as well as the linear, methyl-branched and cyclic constituents for both ends.
The molecular weight of the assessed structures of the UVCB substance Esterification products of Guerbet alcohols, C24-26, branched and cyclic with benzene-1,2,4-tricarboxylic acid 1,2-anhydride is > 1200, therefore they are outside the range of both, the training set and the validation set.
The functional ester groups of Esterification products of Guerbet alcohols, C24-26, branched and cyclic with benzene-1,2,4-tricarboxylic acid 1,2-anhydride (Ester (-C-CO-O-C-) or (HCO-O-C)) are represented in the training set. The maximum occurrence of ester groups per structure in the training set is 2, therefore only two of the three ester groups are addressed by fragment correction.
As a result, the structures used to assess Esterification products of Guerbet alcohols, C24-26, branched and cyclic with benzene-1,2,4-tricarboxylic acid 1,2-anhydride would be considered outside the estimation domain. In addition, the logKow based Koc estimates will be less accurate as the calculated logKow values are > 30, which is far above the reliable prediction range. These values will be associated with a high uncertainty.
Nevertheless, the predictions clearly show that the resulting Koc values are far above 5000 L/kg which is the threshold to conclude on immobility in soil according to McCall et al. (1981) independent of the MW and the branching.

6. ADEQUACY OF THE RESULT
The Koc values were calculated as 1e+010 L/kg and >4e+019 L/kg based on Molecular Connectivity Index (MCI) and log Kow method, respectively. These results both indicate that Esterification products of Guerbet alcohols, C24-26, branched and cyclic with benzene-1,2,4-tricarboxylic acid 1,2-anhydride is highly immobile in soil. Even though the assessed structures are outside the model domain, the estimated Koc values can still be considered indicative of a high immobility in soil, considering the molecular size, weight and structure.
In addition, the available experimental results for the category, these findings support the conclusion that the adsorption potential increases with increasing carbon chain length.
Hence, the KOCWIN predicted adsorption/desorption potential is considered adequate for the purpose of risk assessment.

Documentation of the KOCWIN model is provided in the following references:
Doucette, W.J. 2000. Soil and sediment sorption coefficients. In: Handbook of Property Estimation Methods, Environmental and Health Sciences. R.S. Boethling & D. Mackay (Eds.), Boca Raton, FL: Lewis Publishers (ISBN 1 -56670 -456 -1).
Meylan, W., P.H. Howard and R.S. Boethling. 1992. Molecular topology/fragment contribution method for predicting soil sorption coefficients. Environ. Sci. Technol. 26: 1560 -1567.
McFarland, M. et al. 2007. “Science Advisory Board (SAB) Review of the Estimation Programs Interface Suite (EPI SuiteTM)”. SRC. 1991. Group Contribution Method for Predicting Soil Sorption Coefficients. William Meylan & Philip H. Howard, Syracuse Research Corporation (June 3, 1991). EPA Contract No. 68-D8-0117 (Work Assignment 2-19); SRC F0118-219

Guideline:

other: REACH Guidance on QSARs and grouping of substances R.6

Principles of method if other than guideline:

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).

Specific details on test material used for the study:

SMILES 1: CCCCCCCCCCCCC(CCCCCCCCCC)COC(=O)c1ccc(c(c1)C(=O)OCC(CCCCCCCCCC)CCCCCCCCCCCC)C(=O)OCC(CCCCCCCCCC)CCCCCCCCCCCC [C24 Guerbet alcohols based]
SMILES 2: CCCC(C)CCCCC(C)CC(CCCC(C)CCCCC)COC(=O)c1ccc(c(c1)C(=O)OCC(CCC(C)CCCCCC)CCCCC(C)CCCCCC)C(=O)OCC(CCCC(C)CCCCC)CCC(C)CCCCC(C)CC [branched C24 Guerbet alcohols based]
SMILES 3: C1CCCCC1CCCCC(CCCCCCC1CCCCC1)COC(=O)c1cc(c(cc1)C(=O)OCC(CCCCCCC1CCCCC1)CCCC1CCCCCC1)C(=O)OCC(CCCCCCC1CCCCC1)CCCC1CCCCCC1 [cyclic C24 Guerbet alcohols based]
SMILES 4: CCCCCCCCCCCCCC(CCCCCCCCCCC)COC(=O)c1ccc(c(c1)C(=O)OCC(CCCCCCCCCCC)CCCCCCCCCCCCC)C(=O)OCC(CCCCCCCCCCC)CCCCCCCCCCCCC [C26 Guerbet alcohols based]
SMILES 5: CCCCCC(C)CCCC(C)CC(CCCC(C)CCCCCC)COC(=O)c1ccc(c(c1)C(=O)OCC(CCCC(C)CCCCCC)CCC(C)CCCCC(C)CCC)C(=O)OCC(CCCC(C)CCCCCC)CC(C)CCCCCC(C)CCC [branched C26 Guerbet alcohols based]
SMILES 6: C1CCCCC1CCCCCC(CCCCCCCC1CCCCC1)COC(=O)c1cc(c(cc1)C(=O)OCC(CCCCCCCC1CCCCC1)CCCCC1CCCCCC1)C(=O)OCC(CCCCCCCC1CCCCC1)CCCCCC1CCCCC1 [cyclic C26 Guerbet alcohols based]

Key result

Type:

Koc

Value:

> 10 000 000 000 L/kg

Remarks on result:

other: estimate from MCI

Key result

Type:

Koc

Value:

> 40 000 000 000 000 000 000 L/kg

Remarks on result:

other: estimate from log Kow

KOCWIN v2.01 predicted that representative structures of Esterification products of Guerbet alcohols, C24-26, branched and cyclic with benzene-1,2,4-tricarboxylic acid 1,2-anhydride hava a Koc

1e+010 L/kg (>1e+010 L/kg MCI method; >4e+019 L/kg logKow based method).

Executive summary:

The Koc values for representative structures were calculated as 1e+010 L/kg and >4e+019 L/kg based on Molecular Connectivity Index (MCI) and log Kow method, respectively. These results both indicate that the constituents of Esterification products of Guerbet alcohols, C24-26, branched and cyclic with benzene-1,2,4-tricarboxylic acid 1,2-anhydride are highly immobile in soil. Even though the assessed structures are outside the model domain, the estimated Koc values can still be considered indicative of a high immobility in soil, considering the molecular size, weight and structure.

Description of key information

The constituents of Esterification products of Guerbet alcohols, C24-26, branched and cyclic with benzene-1,2,4-tricarboxylic acid 1,2-anhydride are highly immobile in soil.

Key value for chemical safety assessment

Koc at 20 °C:

10 000 000 000

Additional information

The Koc values were calculated as 1e+010 L/kg and >4e+019 L/kg based on Molecular Connectivity Index (MCI) and log Kow method, respectively. These results indicate that Esterification products of Guerbet alcohols, C24-26, branched and cyclic with benzene-1,2,4-tricarboxylic acid 1,2-anhydride is highly immobile in soil. Even though the assessed structures are outside the model domain, the estimated Koc values can still be considered indicative of a high immobility in soil, considering the molecular size, weight and structure.

In addition, the available experimental results for the category, these findings support the conclusion that the adsorption potential increases with increasing carbon chain length.

Hence, the KOCWIN predicted adsorption/desorption potential is considered adequate for the purpose of risk assessment.

One of the two supporting studies was performed in order to estimate the adsorption coefficient on soil and sewage sludge of the analogue substance 1,2,4 -Benzenetricarboxylic acid, decyl octyl ester (CAS No. 67989 -23 -5) / 1,2,4 -Benzenetricarboxylic acid, mixed decyl and octyl triesters (CAS No. 90218 -76 -1) using the HPLC-method according to OECD Guideline for the Testing of Chemicals No. 121. The log KOC is estimated to be > 5.67. In the second supporting study conducted according to OECD 121 a similar value of > 5.63 was found. These values further support the conclusion that also the constituents of Esterification products of Guerbet alcohols, C24-26, branched and cyclic with benzene-1,2,4-tricarboxylic acid 1,2-anhydride will be immobile in soil.

Hence, the KOCWIN predicted adsorption/desorption potential is considered adequate for the purpose of risk assessment.