1,2-Benzenedicarboxylic acid, di-C8-10-alkyl esters

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 v2.00
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
SMILES: CCCCCCCCCCOC(=O)c1ccccc1C(=O)OCCCCCCCC;
CCCCCCCCCCOC(=O)c1ccccc1C(=O)OCCCCCCCCCC;
CCCCCCCCOC(=O)c1ccccc1C(=O)OCCCCCCCC

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
A reliable QSAR model was used to calculate the adsorption/desorption potential of the 1,2-Benzenedicarboxylic acid, di-C8-10-alkyl ester isomers. Koc values were calculated using the KOCWIN v2.00 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 LogKow methodology.
- Mechanistic interpretation
The methodology and relationship between the first order molecular connectivity index (MCI) and
adsorption coefficient is outlined in the reference paper: Meylan et al., 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
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). The molecular weight range of the 1,2-Benzenedicarboxylic acid, di-C8-10- alkyl ester isomers is 390 - 447, which falls within the range of the training and the validation set.
In addition, the two ester bonds (-C-CO-O-C-) / (HCO-O-C) are represented in the training set and hence addressed by fragment correction.

--------------------------- KOCWIN v2.01 Results ---------------------------
Koc Estimate from MCI:
First Order Molecular Connectivity Index: 14.702 (C8-C10), 15.702 (C10-C10), 13.702 (C8-C8)
Corrected Log Koc: 5.6700 (C8-C10), 6.1913 (C10-C10), 5.1487 (C8-C8)
Estimated Koc(C8-C10): 4.677e+005 L/kg
Estimated Koc(C10-C10): 1.553e+006 L/kg
Estimated Koc(C8-C8): 1.408e+005 L/kg

Koc Estimate from Log Kow:
Log Kow (Kowwin estimate): 9.52 (C8-C10), 9.05 (C10-C10), 8.54 (C8-C8)
Corrected Log Koc : 6.0597 (C8-C10), 5.7997 (C10-C10), 5.5176 (C8-C8)
Estimated Koc(C8-C10): 1.147e+006 L/kg
Estimated Koc(C10-C10): 6.306e+005 L/kg
Estimated Koc(C8-C8): 3.293e+005 L/kg

Fragment Correction(s):
2 Ester (-C-CO-O-C-) or (HCO-O-C) ...... : -0.1312

Experimental Database Structure Match:
Name : DIOCTYL PHTHALATE
CAS Num : 000117-84-0
Exp LogKoc: 4.38
Exp Ref : Schuurmann,G et al (2006)

As a result the 1,2-Benzenedicarboxylic acid, di-C8-10- alkyl ester isomers would not be considered outside the estimation domain.


6. ADEQUACY OF THE RESULT
The Koc values were calculated as 4.677e+005 L/kg, 1.553e+006 L/kg and 1.408e+005 L/kg for the C8-C10, C10-C10 and C8-C8 isomers, respectively, based on Molecular Connectivity Index (MCI). The calculated Koc values based on the logKow method are 1.147e+006 L/kg (C8-C10), 6.306e+005 L/kg (C10-C10), and 3.293e+005 L/kg (C8-C8). These results all indicate that the 1,2-Benzenedicarboxylic acid, di-C8-10- alkyl ester isomers is immobile in soil. These results are supported by the expert database structure match for di-n-octyl phthalate, which reports a logKoc of 4.38.
Hence, the KOCWIN predicted adsorption/desorption potential is considered valid and adequate for the purpose of risk assessment.

7. BIBLIOGRAPHY
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
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Guideline:

other: REACH Guidance on QSARs 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:CCCCCCCCCCOC(=O)c1ccccc1C(=O)OCCCCCCCC; CCCCCCCCCCOC(=O)c1ccccc1C(=O)OCCCCCCCCCC; CCCCCCCCOC(=O)c1ccccc1C(=O)OCCCCCCCC

Key result

Type:

Koc

Value:

467 700 L/kg

Remarks on result:

other: estimate from MCI

Remarks:

C8-C10 isomer

Key result

Type:

Koc

Value:

1 553 000 L/kg

Remarks on result:

other: estimate from MCI

Remarks:

C10-C10 isomer

Key result

Type:

Koc

Value:

140 800 L/kg

Remarks on result:

other: estimate from MCI

Remarks:

C8-C8 isomer

The Koc values were calculated as 4.677e+005 L/kg, 1.553e+006 L/kg and 1.408e+005 L/kg for the C8-C10, C10-C10 and C8-C8 isomers, respectively, based on Molecular Connectivity Index (MCI). The calculated Koc values based on the logKow method are 1.147e+006 L/kg (C8-C10), 6.306e+005 L/kg (C10-C10), and 3.293e+005 L/kg (C8-C8).

Conclusions:

The results all indicate that the 1,2-Benzenedicarboxylic acid, di-C8-10- alkyl ester isomers are immobile in soil, according to the McCall classification scheme (Koc>5000).

Description of key information

KOC has been calculated for the isomers of 1,2 -Benzenedicarboxylic acid, di-C8 -10 -alkyl esters using the computer program KOCWIN (v2.00). It is predicted that the isomers have KOC values > 5000 L/kg (MCI method and KOW method.
Based on the McCall classification scheme, all isomers can be considered as immobile in soil (Koc>5000).

The lowest calculated Koc value (MCI method) for one of the isomers is used as key value.

Key value for chemical safety assessment

Koc at 20 °C:

140 800

Additional information

Koc has been calculated for the isomers of 1,2 -Benzenedicarboxylic acid, di-C8 -10 -alkyl esters using the computer program KOCWIN (v2.00). The Koc values were calculated as 4.677e+005 L/kg, 1.553e+006 L/kg and 1.408e+005 L/kg for the C8-C10, C10-C10 and C8-C8 isomers, respectively, based on Molecular Connectivity Index (MCI). The calculated Koc values based on the logKow method are 1.147e+006 L/kg (C8-C10), 6.306e+005 L/kg (C10-C10), and 3.293e+005 L/kg (C8-C8).

The adsorption coefficient (Koc) on soil and on sewage sludge using high performance liquid chromatography (HPLC) was estimated according to OECD 121 and Council Regulation (EC) No. 440/2008, Method C.19 for the structurally related substance 1,2 -benzenedicarboxylic acid, Di-C6 -10 alkyl ester. The respective read-across justification document is available. The LogKoc values for the various isomers of the C6-C10 phthalate were found to be in the range of 5.6 - 10.4 (soil) and 6.3 - 12.1 (sludge).