Octanoic acid, ester with 1,2,3-propanetriol

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

April 2017

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)
KOWWIN v1.68
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CAS-No
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
A reliable QSAR model was used to calculate the partition coefficient of Diisotridecyl adipate. The logKow value was calculated using the KOWWIN v1.68 module embedded within the EPISuite computer model. KOWWIN™ estimates the log octanol-water partition coefficient, log Kow, of chemicals using an atom/fragment contribution method. EPISuite and its modules (including KOWWIN) 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 KOWWIN) have been incorporated into the OECD Toolbox. Inc lusion 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 ongoing input for improvements. KOWWIN is listed as one of the QSARs for use in predicting partition coefficient (Kow) of organic compounds values in the literature referenced in Guidance on information requirements and chemical safety assessment Chapter R.7a: Endpoint specific guidance. In summary, the EPISuite modules (including KOWWIN) have had their scientific validity established repeatedly.
https://www.epa.gov/tsca-screening-tools/epi-suitetm-estimation-program-interface

- Defined endpoint and unambiguous algorithm:
KOWWIN uses a "fragment constant" methodology to predict log P. In a "fragment constant" method , a structure is divided into fragments (atom or larger functional groups) and coefficient values of each fragment or group are summed together to yield the log P estimate. KOWWIN’s methodology is known as an Atom/Fragment Contribution (AFC) method. Coefficients for individual fragments and groups were derived by multiple regression of 2447 reliably measured log P values. KOWWIN’s
"reductionist" fragment constant methodology (i.e. derivation via multiple regression) differs from the "constructionist" fragment constant methodology of Hansch and Leo (1979) that is available in the CLOGP Program (Daylight, 1995). See the Meylan and Howard (1995) journal article for a more complete description of KOWWIN’s methodology.
- Defined domain of applicability:
According to the KOWWIN 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 ranges of the training set compounds and 2) and/or that have more instances of a given fragment than the maximum for all training set compounds. It is also possible that a compound may have a functiona
l group(s) or other structural features not represented in the training set, and for which no fragment coefficient was developed.
- Appropriate measures of goodness-of-fit and robustness and predictivity:
Total Training Set Statistics: Number of substances in dataset = 2447, Correlation coef (r2) = 0.982, Standard deviation = 0.217, Absolute deviation = 0.159, Avg. Molecular Weight = 199.98.
Training Set Estimation Error: within ≤ 0.10 - 45.0%, within ≤0.20 - 72.5%, within ≤ 0.40 - 92.4%, within ≤ 0.50 - 96.4%, within ≤ 0.60 - 98.2%.

The KOWWIN predicted partition coefficient value is considered valid and fit for purpose.

BIBLIOGRAPHY
Documentation of the KOWWIN model is provided in the following references:
Akamatsu, M., Y. Yoshida, H. Nakamura, M. Asao, H. Iwamura and T. Fujita. 1989. Hydrophobicity of di- and tripeptides having un-ionizable side-chains and correlation with substituent and structural parameters. Quant. Struct.-Act. Relat. 8: 195-203.
Akamatsu, M., S.I. Okutani, K. Nakao, N.J. Hong and T. Fujita. 1990. Hydrophobicity of N-acetyl, di- and tripeptide amides having unionizable side chains and correlation with substituent and structural parameters. Quant. Struct.Act. Relat., 9: 189-194.
Akamatsu, M. and T. Fujita. 1992. Quantitative analyses of hydrophobicity of di- to pentapeptides having nonionizable side chains with substituent and structural parameters, J. Pharm. Sci. 81: 164-174.
Barbato, F., G. Caliendo, M.I. LaRotonda, P. Morrica, C. Silipo and A. Vittoria. 1990. Relationships between octanol-water partition data, chromatographic indexes and their dependence on pH in a set of beta-adrenoceptor blocking agents. Farmaco, 45:, 647-663.
Daylight. 1995. CLOGP Program. Daylight Chemical Information Systems. Von Karman Ave.,Irvine, CA 92715. (web-site as of March 2008: http://www.daylight.com/)
Hansch, C and Leo, A.J. 1979. Substituent Constants for Correlation Analysis in Chemistry and Biology; Wiley: New York, 1979.
Hansch. C., A. Leo and D. Hoekman. 1995. Exploring QSAR. Hydrophobic, Electronic, and Steric Constants. ACS Professional Reference Book. Washington, DC: American Chemical Society.
Howard, P.H. and M. Neal. 1992. Dictionary of Chemical Names and Synonyms. Lewis Publishers, Chelsea, MI (ISBN 0-87371-396-6)
Meylan, W.M. and P.H. Howard. 1995. Atom/fragment contribution method for estimating octanol-water partition coefficients. J. Pharm. Sci. 84: 83-92.
Meylan, W.M. P.H. Howard and R.S. Boethling. 1996. Improved method for estimating water solubility from octanol/water partition coefficient. Environ. Toxicol. Chem. 15: 100-106.
Meylan, WM, Howard, PH, Boethling, RS et al. 1999. Improved Method for Estimating Bioconcentration / Bioaccumulation Factor from Octanol/Water Partition Coefficient, Environ. Toxicol. Chem. 18(4): 664-672.
Meylan, W.M. and P.H. Howard. 2005. Estimating octanol-air partition coefficients with octanol-water partition coefficients and Henry's law constants. Chemosphere 61:640-644.
Morrison, R.T. and R.N. Boyd. 1973. Organic Chemistry. Third Ed., Boston, MA: Allyn and Bacon, Inc. p. 1133-38.
Nieder, M., W. Stroesser and J. Kappler. 1987. Octanol/buffer partition coefficients of different betablockers", Arzneim.- Forsch., 37: 549-550.
Ribo, J.M. 1988. The octanol/water partition coefficient of the herbicide chlorsulfuron as a function of pH. Chemosphere 17: 709-15.
Sangster, J. 1994. LOGKOW Databank. A databank of evaluated octanol-water partition coefficients (Log P) on microcomputer diskette. Montreal, Quebec, Canada: Sangster Research Laboratories. Current Internet access available at: http://logkow.cisti.nrc.ca/logkow/index.jsp
Streitwieser, A. Jr. and C.H. Heathcock. 1985. Introduction to Organic Chemistry. Third Ed., NY: Macmillan Publ. Co. p. 926-32.
Takacs-Novak, K., M. Jozan and G. Szasz. 1995. Lipophilicity of amphoteric molecules expressed by the true partition coefficient. International J. Pharm. 113: 47-55.
US EPA. 1992. Dermal Exposure Assessment: Principles and Applications. EPA/600/8-91-011B, January 1992, Interim Report. U.S. Environmental Protection Agency, Exposure Assessment Group, Office of Health and Environmental Assessment, Washington, DC.
US EPA. [2012]. Estimation Programs Interface Suite™ for Microsoft® Windows, v 4.11. United States Environmental Protection Agency, Washington, DC, USA.
Yamana, T., A. Tsuji, E. Mikyamoto and O. Kubo. 1977. Novel method for determination of partition coefficients fo penicillins and cephalosporins by high-pressure liquid chromatography. J. Pharm. Sci. 66: 747-9.

Principles of method if other than guideline:

- Software tool(s) used including version: EPISuite v4.11
- Model(s) used: KOWWIN v1.68
- Method description: Log Pow is calculated using a "fragment constant" methodology. the test substance structure is divided into fragments (atom or larger functional groups) and coefficient values of each fragment or group are summed together to yield the log P estimate.
- Justification of QSAR prediction: see field 'Justification for type of information'

Type of method:

calculation method (fragments)

Partition coefficient type:

octanol-water

Specific details on test material used for the study:

Octanoic acid, ester with 1,2,3-propanetriol contains 50% octanoic acid, monoester with glycerol (26402-26-6), 40% dioctanoic acid, diester with glycerol (36534-80-0), 10% glycerol trioctanoate (538-23-8).

Key result

Type:

log Pow

Partition coefficient:

3.8

Temp.:

25 °C

Remarks on result:

other: calculated (KOWWIN v1.68)

CAS Number: 26402-26-6

SMILES : O=C(OCC(O)CO)CCCCCCC

CHEM   : Octanoic acid, monoester with 1,2,3-propanetriol

MOL FOR: C11 H22 O4

MOL WT : 218.30

Log Octanol-Water Partition Coef (SRC):

Log Kow (KOWWIN v1.68 estimate) =  1.71

CAS Number: 36354-80-0

SMILES : CCCCCCCC(=O)OCC(O)COC(=O)CCCCCCC

CHEM   :

MOL FOR: C19 H36 O5

MOL WT : 344.50

Log Octanol-Water Partition Coef (SRC):

Log Kow (KOWWIN v1.68 estimate) =  5.25

CAS Number: 538-23-8

SMILES : O=C(OCC(OC(=O)CCCCCCC)COC(=O)CCCCCCC)CCCCCCC

CHEM   : Octanoic acid, 1,2,3-propanetriyl ester

MOL FOR: C27 H50 O6

MOL WT : 470.70

Log Octanol-Water Partition Coef (SRC):

Log Kow (KOWWIN v1.68 estimate) =  9.20

Weighted Average log Kow = (0.5*1.71) + (0.4*5.25) + (0.1*9.20) = 3.8

Conclusions:

The estimated logKow (calculation based on fragment contribution) was 3.8. The KOWWIN predicted partition coefficient value is considered valid and fit for purpose.

Executive summary:

Log Kow for Octanoic acid, ester with 1,2,3-propanetriold was calculated using the Atom/Fragment Contribution (AFC) method. With the program KOWWIN v1.68 (part of US EPA EPI Suite v4.11), a log Kow of 3.8 was

determined.

Key value for chemical safety assessment

Log Kow (Log Pow):

3.8

at the temperature of:

25 °C