Tangor, Murcote, ext.

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Values for individual constituents of this natural complex substance (NCS) were calculated using a validated QSAR. All constituents fall within the applicability domain of the QSAR.

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: REACH Guidance on QSARs R.6

Deviations:

not applicable

Principles of method if other than guideline:

The partition coefficient of a NCS has little meaning. The range of Log Kow was based on empirical results for limonene and for the constituents the results were predicted based on structural molecular fragments by the KOWWIN program of EPIWIN.

Calculated and measured data on the constituents are obtained from Kowwin v1.67. Figure 1 (attached as a picture) shows that most measured values are lower than the estimated values. It is also clear from the figure that for many constituents, measured log Kow values vary. Sometimes this variation is more than one log unit, especially for the more hydrophobic constituents with a log Kow > 4. It is generally recognized that the log Kow determination of more hydrophobic substances is easily prone to experimental flaws and that for this group it is important to use adequate methods designed to determine higher log Kow values.

This is considered valid because of the variation of measured log Kow values for the constituents, the unknown method of determination and because the calculated log Kow are generally more conservative (higher) than the measured log Kow.

GLP compliance:

no

Type of method:

other: calculation by estimation and empirical for major constituent

Partition coefficient type:

octanol-water

Key result

Type:

log Pow

Partition coefficient:

>= 3.38 - <= 4.88

Temp.:

25 °C

Remarks on result:

other: pH not measured, because of in-silico study

Details on results:

No data

Substance	CAS	Estimated log Kow
D-limonene	5989-27-5	4.38 (measured, Griffin et al 1999)
γ-terpinene	99-85-4	4.75
Myrcine B	123-35-3	4.88
alpha-pinene	7785-70-8	4.27
Beta-Pinene	127-91-3	4.35
Linalool	78-70-6	3.38
Citral	5392-40-5	3.45
Decanal	112-31-2	3.76

Kowwin v1.67a model details

Reference to the type of model used

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™s methodology is known as an Atom/Fragment Contribution (AFC) method.

 

Description of the applicability domain

The applicability domain is based on the maximum number of instances of that a fragment can be used in a chemical and molecular weight. The minimum and maximum values for molecular weight are the following:

 

Training Set Molecular Weights:

Minimum MW: 18.02

Maximum MW: 719.92

Average MW: 199.98

 

Validation Molecular Weights:

Minimum MW: 27.03

Maximum MW: 991.15

Average MW: 258.98

Currently there is no universally accepted definition of model domain. However, users may wish to consider the possibility that log P estimates are less accurate for compounds outside the MW range of the training set compounds, 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 functional group(s) or other structural features not represented in the training set, and for which no fragment coefficient was developed. These points should be taken into consideration when interpreting model results.

 

Description and results of any possible structural analogues of the substance to assess reliability of the prediction

External validation with a dataset containing 10946 substances resulted in a correlation coefficient (r²) of 0.943, a standard deviation of 0.479 and an absolute deviation of 0.358.

Predictivity assessment of the external validation set:

Validation Set Estimation Error:

within <= 0.20 - 39.6%

within <= 0.40 - 66.0%

within <= 0.50 - 75.6%

within <= 0.60 - 82.5%

within <= 0.80 - 91.6%

within <= 1.00 - 95.6%

within <= 1.20 - 97.7%

within <= 1.50 - 99.1%

Uncertainty of the prediction

All constituents for which estimations were made fall within the applicability domain of the model.

Mechanistic domain

KOWWIN (the Log Octanol-Water Partition Coefficient Program) estimates the logarithmic octanol-water partition coefficient (log P) of organic compounds. KOWWIN requires only a chemical structure to estimate a log P. The octanol-water partition coefficient is a physical property used extensively to describe a chemical's lipophilic or hydrophobic properties. It is the ratio of a chemical's concentration in the octanol-phase to its concentration in the aqueous phase of a two phase system at equilibrium. Since measured values range from less than 10^-4 to greater than 10^8 (at least 12 orders of magnitude), the logarithm (log P) is commonly used to characterize its value.

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™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.

As all regular and common fragments are included in this method, and the constituents for which this method was applied do not contain exotic fragments, there are no limits to the mechanistic domain.

Conclusions:

The log Kow range of the constituents of tangerine oil is 3.38 - 4.88. The percentage of known constituents with log Kow > 4 is 94%.

Executive summary:

Log Kow was estimated for the constituents of Tangerine Oil using the program KOWWIN of EPIWIN. The validity of the approach was checked by comparison of measured and predicted values for related substances. Only for the main constituent limonene the empirical log Kow was used.

The log Kow range for tangerine oil constituents was found to be 3.38 - 4.88. The percentage of known constituents with log Kow > 4 is 94%.

Description of key information

The log Kow range of the known constituents of tangerine oil is 3.38 - 4.88. The percentage of known constituents with log Kow > 4 is 94%.

Additional information

The log Kow range of the known constituents of tangerine oil is 3.38 - 4.88. The percentage of known constituents with log Kow > 4 is 94%.

The major constituent limonene has a reported measured Log Kow value of 4.38.