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Partition coefficient

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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:
reference to other study
Principles of method if other than guideline:
QSAR estimation
Partition coefficient type:
octanol-water
Type:
log Pow
Partition coefficient:
>= 5.33 - <= 6.42
Remarks on result:
other: Temperature and pH not provided (QSAR estimation)
Remarks:
Range of logKow estimated on a the known constituents of the substance (13.5% 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 214 .3 and 260.34 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 

Aromatic carbon

 0.2940

24 

1790 

30 

8792 

Aromatic oxygen

 -0.0423

 2

69 

 334

-tert Carbon [3 ot more carbon attach]

0.2676 

 4

130 

1381 

Fused aliphatic ring unit correction

 -0.3421

 41

684 

 =CH2 [olefinic carbon]

 0.5184

50 

235 

  C [aliphatic carbon-No H, not tert]

 0.9723

 3

242 

11 

1361 

  -O- [oxygen, aliphatic attach]

 -1.2566

108 

12 

1235 

  -C(=O)O [ester, aliphatic attach]

-0.9505 

113 

 1178

 

Conclusions:
Log Kow of known constituents of the substance, representing 13% of the composition, were estimated to be between 5.33 and 6.42 (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 (only 13% of the composition) were estimated using the recommended QSAR model KOWWIN v1.68, based on Atom/Fragment Contribution (AFC) method. The constituents of the test item were within the applicability domain (MW, descriptors).

This range of logKow was estimated between 5.33 and 6.42, with a standard deviation provided by the model of 0.48.

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 its 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.
The two first 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). The third strategy based on the application of the OECD 123 method and the quantification of the test item in both octanol and water phases by a GC-FID analytical method did not allow to detect the totality of the test item constituents.
Finally the application of the conventional Log Pow determination methods is limited due to the limited knowledge of composition of the test item.
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) makes the log Kow determination extremely difficult. The purpose of this feasibility study was to evaluate different methodologies that could be applied for the determination of the Partition of the test item. Various approaches were considered in this study and the results are presented in this report.
The two first strategies tested were the application of the OECD 117 method : "Partition Coefficient (n-octanol/water), HPLC method". The analytical system used was composed of an HPLC system coupled firstly to a Diode Array Detector and secondly to a mass spectrometer.
Then, another strategy is tested in order to consider the use of OECD 123 method and the analytical determination of the substance in water and in octanol phases by a GC-FID analytical method to determine the log Kow.
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 (100mg/L) and the injection volume selected (300µL) 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 large peak was observed at low retention time, some peaks were observed around a retention time corresponding to a log Pow around 4 and peaks were observed after a retention time corresponding to log Pow > 5.5.

It has to be reminded that these log Pow estimations might correspond to minor constituents that lead to a detector response with a DAD. These 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 10 min, on both sides of two "reference" compounds, i.e. tebuconazole with a logKow = 3.3 and propargite with a logKow = 5.8 eluted at 6.9min and 8.8 min respectively using the same method.

=> Unfortunately, this HPLC-MS method did not allow 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.

3. Applicability of the OECD 123 method

It can be observed that all the detectable chromatographic peaks are eluted between de C10 and the C40 reference peaks. The hydrocarbon index measured was 10.7 mg/L whereas the theoretical concentration was 61.75 mg/L. That means that only 10.70 / 61.75 = 17.3% of the test item is visible with this analytical technique.

Conclusions:
The feasibility study showed that, under the experimental conditions tested, no reliable range of logKow can be determined using OECD 117 or OECD 123 methods.
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:

Three strategies for the determination of the partition coefficient n-octanol/water were assessed.

The two first 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).

The third strategy based on the application of the OECD 123 method and the quantification of the test item in both octanol and water phases by a GC-FID analytical method did not allow to detect the totality of the test item constituents.

Finally, this feasibility study confirms that none of the three approaches investigated allows 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.

Description of key information

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

Key value for chemical safety assessment

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. 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 13% 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).