Registration Dossier

Physical & Chemical properties

Partition coefficient

Currently viewing:

Administrative data

Link to relevant study record(s)

Referenceopen allclose all

Endpoint:
partition coefficient
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Study period:
run on 2018
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:
>= 1.58 - <= 6.52
Remarks on result:
other: Temperature and pH not provided (QSAR estimation)
Remarks:
Range of logKow estimated on a the known constituents 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 124.14 and 344.32 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 & Correction Factor 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
-COOH   [acid, aliphatic attach]  -0,6895 3 126 3 672
-tert Carbon [3 or more carbon attach] 0,2676 4 130 8 1381
Fused aliphatic ring unit correction  -0,3421 8 41 8 684
Aromatic carbon 0,294 24 1790 30 8792
-O-   [oxygen, one aromatic attach]  -0,4664 3 203 5 1770
-OH     [hydroxy, aromatic attach] -0,4802 3 193 4 611
Ortho-Hydroxy to misc. -C(=O)- correction  0,777 2 11 2 82
-C(=O)- [carbonyl, aliphatic attach] -1,5586 2 54 2 241
-C(=O)O [ester, aromatic attach] -0,7121 2 88 2 414
ring reaction -> -OH ortho to ester 1,2556 1 20 1 13
-C(=O)- [carbonyl, one aromatic attach] -0,8667 2 51 2 232
-C(=O)- [carbonyl, olefinic attach] -1,27 2 43 2 401
-Cl [chlorine, aromatic attach] 0,6445 6 318 10 1483
-CHO    [aldehyde, aromatic attach] -0,2828 1 13 1 54
Conclusions:
Log Kow of known constituents of the substance, representing a limited fraction of the composition, were estimated to be between 1.58 and 6.52 (estimated by QSAR)
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 test item were within the applicability domain (MW, descriptors).

This range of logKow was estimated between 1.58 and 6.52, with a standard deviation provided by the model of 0.48.

Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Study period:
13 - 15 November 2017
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
unsuitable test system
Justification for type of information:
A study has been conducted according to OECD 117 leading to a result partially not reliable, i.e. more than 30% of the substance has a logKow < 0.3 while the substance is know to be insoluble in water. In addition, % area is not necessarily correlated to absolute concentration if UV detection is used. Therefore we cannot guarantee the repartition of the logPow in the composition of the substance and that the results obtained by HPLC/DAD are representative of the whole substance. Therefore this conventional standard test for partition coefficient endpoint is considered as not appropriate for such complex substances.
Qualifier:
according to
Guideline:
OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)
Version / remarks:
2004
Deviations:
no
Qualifier:
according to
Guideline:
other: Regulation (EU) No 2016/266 of 7 December 2015, Method A.24 “Partition coeffi-cient(n-octanol/water), high performance liquid chromatography (HPLC) method”.
Version / remarks:
2015/2016
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
inspected on 13-14 October 2014 / signed on 08 April 2015
Type of method:
HPLC method
Partition coefficient type:
octanol-water
Type:
log Pow
Partition coefficient:
< 0.3
Temp.:
25 °C
pH:
ca. 6.11
Remarks on result:
not determinable because of methodological limitations
Remarks:
Peak 1, 2, 3 corresponding to about 30% of the peak area (mean of three measurements). For peak 1 and 2, the retention time of peak 1 and 2 is lower than the retention time of thiourea, which was used for the determination of the dead time of the method. therefore log Kow was not calculable (k is negative). So the log POW of peak 1, 2 and 3 is stated as < 0.3. As the calculated log POW of peak 3 lay below the lowest log POW of the reference items (2-Butanone with log POW 0.3), the log POW of this peak is stated as < 0.3.
Type:
log Pow
Partition coefficient:
1.404
Temp.:
25 °C
pH:
ca. 6.11
Remarks on result:
other:
Remarks:
peak 4 corresponding to about 4.57% of the peak area (mean of three measurements).
Type:
log Pow
Partition coefficient:
1.787
Temp.:
25 °C
pH:
ca. 6.11
Remarks on result:
other:
Remarks:
peak 5 corresponding to about 5.78% of the peak area (mean of three measurements).
Type:
log Pow
Partition coefficient:
2.308
Temp.:
25 °C
pH:
ca. 6.11
Remarks on result:
other:
Remarks:
peak 6 corresponding to about 1.21% of the peak area (mean of three measurements).
Type:
log Pow
Partition coefficient:
2.602
Temp.:
25 °C
pH:
ca. 6.11
Remarks on result:
other:
Remarks:
peak 7 corresponding to about 32.11% of the peak area (mean of three measurements).
Type:
log Pow
Partition coefficient:
2.802
Temp.:
25 °C
pH:
ca. 6.11
Remarks on result:
other:
Remarks:
peak 8 corresponding to about 16.65% of the peak area (mean of three measurements).
Type:
log Pow
Partition coefficient:
3.801
Temp.:
25 °C
pH:
ca. 6.11
Remarks on result:
other:
Remarks:
peak 9 corresponding to about 8.09% of the peak area (mean of three measurements).
Type:
log Pow
Partition coefficient:
4.631
Temp.:
25 °C
pH:
ca. 6.11
Remarks on result:
other:
Remarks:
peak 10 corresponding to about 1.58% of the peak area (mean of three measurements).

Results:

Reference item:

For each reference item, the retention times, the calculated capacity factors k, logk and log Kow were presented in the following table:

Compound Mean Retention Time (min) k log k log POW
Thiourea 1,392 0    
2-Butanone 1,833 0,3174 -0.4985 0.30
Benzylalcohol 2,157 0,5499 -0.2597 1.10
Acetophenone 2.649 0,9032 -0.0442 1.70
Nitrobenzene 3,117 1,2395 0.0932 1.90
Benzene 4.358 2,1317 0.3287 2.10
Toluene 6.743 3,8452 0.5849 2.70
 Naphtalene  9.251  5.6475  0.7519 3.60
 Phenanthrene  21.985  14.7968  1.1702 4.50

Dead time is 1.392 ± 0.000 minutes, with RSD 0.006%.

The RSD of the retention times of the reference items lay all below 0.5 %.

Equation of the regression:

log k = 0.4069 * log POW – 0.6446 with a coefficient of determination r2 = 0.9766

Test item:

Retention Times Test Item

Measurement

RT 1

RT 2

RT 3

RT 4

RT 5

RT 6

 

min.

min.

min.

min.

min.

min.

Mean of three measurements

1.156

1.297

1.717

2.567

3.075

4.133

Standard Deviation

0.005

0.005

0.000

0.000

0.000

0.000

Measurement

RT 7

RT 8

RT 9

RT 10

 

 

min.

min.

min.

min.

 

Mean of three measurements

5.003

5.747

12.497

25.567

 

Standard Deviation

0.005

0.010

0.005

0.014

 

Capacity Factor, log Capacity Factor, log POW of test Item peaks were provided in the report.

log POWwas calculated from the capacity factor as follows:

 

log POW= (log K + 0.6446) / 0.4069

Executive summary:

The partition coefficient of the test substance was measured according to the OECD 117/EU A8 guideline, HPLC method. The system was calibrated with eight different reference substances.

The correlation log K / log POWwas used for the calculation of the log POWof the constituents of test item visible by HPLC-DAD.

Correlation log k/Log POW is good (r² = 0.9766).

Due to the fact that the retention time of peak 1 and 2 lay below the retention time of thiourea (log POWis not calculable) and the calculated log POWof peak 3 was lower than the lowest log POWof the reference items (2-Butanone with log POW0.3) the log POWof these peaks is stated as < 0.3.

Based on peak area, the peaks showing a logKow < 0.3 correspond to about 30% of detected peaks. 68.4% of detected peaks show a logKow between 1.4 and 3.80 and one peak of 1.6% has a logKow at about 4.6.

Note that % area is not necessarily correlated to absolute concentration if UV detection is used. Therefore we cannot guarantee the repartition of the logPow in the composition of the substance and that the results obtained by HPLC/DAD are representative of the whole substance.

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 contains constituents which are mostly unkown and its physical state leads to difficulties for physico-chemical testing: It is described as a dark brown sticky high viscous resin in clumps in different sizes to solid.
A GLP study has been conducted on a similar substance, the Oakmoss concrete according to OECD 117 showing that this method is not appropriate for such complex substances (three peaks of the test item corresponding to more than 30% of the peak area have a logKow < 0.3 while the substance is mainly insoluble in water).
In addition, % area is not necessarily correlated to absolute concentration in the substance if UV detection is used. Therefore we cannot guarantee the repartition of the logPow in the composition of the substance and that the results obtained by HPLC/DAD are representative of the whole substance.
Moreover the physical state and the limited knowledge on the composition of such substances lead to technical issues to quantify the substance dissolved in water or in octanol media (HPLC or GC/FID do not allow to detect the totality of the test item constituents). Then OCDE 107 and 123 are also considered as not appropriate.
Finally conventional standard tests for partition coefficient endpoint intended for single substances are considered as not appropriate for such complex substances.
That is why the test has been waived for the registered substance.
Reason / purpose:
data waiving: supporting information

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

The substance is a complex mixture, which contains constituents which are mostly unkown and its physical state leads to difficulties for physico-chemical testing: It is described as a dark brown sticky high viscous resin in clumps in different sizes to solid.

A GLP study has been conducted on a similar substance, the Oakmoss concrete, according to OECD 117 showing that this method is not appropriate for such complex substances (three peaks of the test item corresponding to more than 30% of the peak area have a logKow < 0.3 while the substance is mainly insoluble in water).

In addition, % area is not necessarily correlated to absolute concentration in the substance if UV detection is used. Therefore we cannot guarantee  the repartition of the logPow in the composition of the substance and that the results obtained by HPLC/DAD are representative of the whole substance.

Moreover the physical state and the limited knowledge on the composition of such substances lead to technical issues to quantify the substance dissolved in water or in octanol media (HPLC or GC/FID do not allow to detect the totality of the test item constituents). Then OCDE 107 and 123 are also considered as not appropriate.

Therefore conventional standard tests for partition coefficient endpoint intended for single substances are considered as not appropriate for such complex substances.

That is why the test has been waived for the registered substance.

Finally calculated values were provided on known constituents of the substance. However, only a range of logKow on a limited part of the composition of the substance 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).