Resinoid of Commiphora erythraea (Burseraceae) obtained from the gum by ethanol extraction

Partition coefficient

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

partition coefficient

Data waiving:

study technically not feasible

Justification for data waiving:

other:

Justification for type of information:

The substance is a complex mixture, which contain a large number of constituents with different solubility (often low solubility) and volatility. In addition, the composition of this complex substance is mostly unknown and their physical state leads to further difficulties for physico-chemical testing: It is (mostly) solid(ish), extremely viscous resins.
Standard tests for partition coefficient endpoint are intended for single substances and are not appropriate for such complex substances.
A feasibility study has been conducted on the test item in order to determine the more suitable standard method to determine the partition coefficient range of the test item.
Two approaches, based on the application of the OECD 117 method, were not applicable due to the very low response of the test item with the HPLC detectors tested (Diode Array Detector and Mass Spectrometry).
Note that the application of other standard methods (such as OECD 123) is limited to the low pourcentage of constituents visible by GC/FID (only about 24% according to internal data, ie. quantification of all detected constituents by internal standard and correction with correction factors).
Finally the application of the conventional Log Pow determination methods is limited due to the limited knowledge of composition of the test item.

Reference 2

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

April to December 2016

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Feasibility study to demonstrate the technical issue in the determination of the partition coefficient of the substance using standard methods

Qualifier:

no guideline followed

Principles of method if other than guideline:

The very complex nature of the test item (UVCB, very viscous, composed of about 80-90% of unknown constituents) make its log Pow determination very challenging. Various approaches were considered in this study to evaluate different methodologies that could be applied for the determination of the Partition Coefficient n-octanol/water (log Pow) of the test item and to establish the feasibility of the study.
The application of the OECD 117 method : "Partition Coefficient (n-octanol/water), HPLC method" was tested. The analytical system used was composed of an HPLC system coupled firstly to a Diode Array Detector and secondly to a Mass Spectrometer.

GLP compliance:

no

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Analytical method:

gas chromatography

high-performance liquid chromatography

mass spectrometry

other: Diode Array Detector

Remarks on result:

not determinable because of methodological limitations

Remarks:

The application of the conventional Log Pow determination methods is not possible with this test item (extremely viscous resinous UVCB substance) due to the nature of the substance and the limited knowledge of its composition.

1. Feasibility by an HPLC-DAD Method

The first observations were that the test item response with this detector was very low even if the test item concentration (100 mg/L) and the injection volume selected (300 µL) were quite high compared to those usually employed. Nevertheless a few chromatographic peaks can be observed. By comparison with the reference compounds, the log Kow of the test item constituents can be estimated. A peak was observed at a retention time, which corresponds to a log Pow around 5.

It has to be reminded that this log Pow estimation might correspond to a minor constituent that lead to a detector response with a DAD. This constituent might not reflect the main composition of the test item.

In order to detect a higher proportion of the test item constituents, a test was conducted with a HPLC-MS method.

2. Feasibility with a HPLC-MS method

Once again, despite the high concentration of the test item, the signal intensities observed were very low compared to a blank injection as well as in ESI+ as in ESI-.

The log Pow values of the weak peaks observed can be estimated by a comparison with the retention times of compounds having a known logKow and that were injected with the same chromatographic method.

Finally a large mass of minor peaks were observed between 2 and 11 min, on both sides of the two "reference" compounds, i.e. tebuconazole with a logKow = 3.3 and propargite with a logKow = 5.8 eluted at 6.9 min and 8.8 min respectively using the same method.

=> Unfortunately, this HPLC-MS method did not allowed to detect a larger proportion of the test item constituents. The very low signal intensity observed is not exploitable for a complete and reliable OECD 117 study.

Conclusions:

The feasibility study showed that, under the experimental conditions tested, no reliable range of logKow can be determined using OECD 117 method.
Considering the results obtained in this study, we can only anticipate that some constituents of the substance have a logKow > 5.
Therefore, the substance has potential for bioaccumulation.

Executive summary:

Two strategies for the determination of the partition coefficient n-octanol/water were assessed based on the application of the OECD 117 method.

This study shows that the standard method is not applicable due to the very low response of the test item with the HPLC detectors tested (Diode Array Detector and Mass Spectrometry).

Finally, this feasibility study confirms that none of the approaches investigated allow to provide an accurate log P value of the test item. It can be concluded that the application of the conventional Log Pow determination methods is not possible with this test item (UVCB, very viscous resin, composed of about 80-90% of unknown constituents) due to the limited knowledge of its composition, i.e. only a limited part of the composition of the substance was detected and quantifiable using the conventional detectors.

Reference 3

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

run on 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 limited documentation / justification

Justification for type of information:

QSAR prediction : The values obtained on known constituents of the substance are not experimental results, however the QSAR model is recommended by the ECHA guidance document on information requirements, is well documented with regard to validation parameters according to OECD principles. Moreover, the constituents of the substance are fully characterised towards the applicability domain.

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

QSAR estimation

Partition coefficient type:

octanol-water

Type:

log Pow

Partition coefficient:

>= 4.8 - <= 7.05

Remarks on result:

other: Temperature and pH not provided (QSAR estimation)

Remarks:

Range of logKow estimated on a the known constituents of the substance (11% of the substance)

Temperature and pH values are not considered in this model.

The estimation is based on the non-ionised form of the molecule.

No Experimental Value Adjustment was made.

The molecular weight of the constituents are between 136.2 and 204.4 g/mol, hence within the estimation domain of the validation set (27.03 -991.15 g/mol), all the functional groups are included in the list of descriptors, and the occurence of each fragment is below the maximum number in the training/validation sets (Appendix D), such as:

		Training Set		Validation Set
Fragment Descriptor	Coef	Max	Number	Max	Number
-CH3    [aliphatic carbon]	0.5473	13	1401	20	7413
-CH2-   [aliphatic carbon]	0.4911	18	1083	28	7051
-CH   [aliphatic carbon]	0.3614	16	460	23	3864
=CH- or =C<  [olefinc carbon]	0.3836	10	239	10	1847
-tert Carbon [3 ot more carbon attach]	0.2676	4	130	8	1381
Fused aliphatic ring unit correction	-0.3421	8	41	8	684
=CH2 [olefinic carbon]	0.5184	2	50	4	235

 

Conclusions:

Log Kow of known constituents of the substance were estimated to be between 4.8 and 7.05 (estimated by QSAR)
The substance should have potential for bioaccumulation and it shall also be taken into account for PBT assessment.

Executive summary:

The partition coefficient of the known constituents of the substance were estimated using the recommended QSAR model KOWWIN v1.68, based on Atom/Fragment Contribution (AFC) method. The constituents of the substance are within the applicability domain (MW, descriptors).

The calculated results were log Kow between 4.8 and 7.05, with a standard deviation provided by the model of 0.48.

Description of key information

No range of logKow representative of the test item as a whole can be determined (neither with an experimental approach nor with an estimation approach).

Additional information

A feasibility study was conducted to demonstrate the technical issue in the determination of the partition coefficient of the substance using standard methods.

Finally only a limited part of the composition of the substance was detected and quantifiable using the conventional detectors and the application of the standards Log Pow determination methods is limited due to the limited knowledge of composition of the test item.

In addition calculated values were provided on known constituents of the substance. However, only a range of logKow on a small part of the composition of the substance (about 11% of the composition) can be calculated using QSAR estimations.

Therefore it is considered that no range logKow representative of the whole test item can be determined (neither with an experimental approach nor with an estimation approach).