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Partition coefficient

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Description of key information

Log Kow = 6.48

Key value for chemical safety assessment

Log Kow (Log Pow):
6.48
at the temperature of:
25 °C

Additional information

PRELIMINARY ESTIMATIONS

 

A preliminary estimation on pure oleamide (C18:1) performed with EPISUITE 4.0 is indicating:

 

Log Kow (KOWWIN v1.68 estimate) = 6.48

 

Further evaluation have been done by comparing the estimated values (KOWWIN v1.68) of the similar compounds and the measured values with HPLC method (reported as Weight of Evidence summaries)

 

 

Calc

Exp

Calc

Exp

C16 sat

5.71

>6.5

C16 uns

5.5

*5.8

C18 sat

6.7

C18 uns

6.48

C20 sat

7.68

C20 uns

7.46

C22 sat

8.66

C22 uns

8.44

>8

                                                 * = shake flask method

 

It can be noticed that in the series C22:0 - C20:0 - C18:0 - C16:0 the value of Log Kow is decreasing regularly from >8 to 5.7 and that the corresponding monounsaturated molecule is predicted 0.2 points lower.

It can be noticed that the estimated value is in good agreement with the measured one with HPLC method. In fact the substance experimentally tested for Log Kow C18 sat. was analytically verified as containing a small % of C16.

If we consider the estimated value a bit higher than the measured one, in has to be considered in a very small range of variability (+/- 0.5)

 

Also the oleamide tested substance with Shake Flask method was analytically identified as containing a % of C16 uns (6.3%), therefore also the estimated value, corrected for the composition could be slightly lower than 6.48 (about 6.41)

Based on the previous considerations, the estimated value for a measurement in HPLC of the Log Kow for Amides C18:1 is within the range of 6.41 ± 0.5, i.e. between 5.91 and 6.91.

 

THE EXPERIMENTAL TEST

 

The test on the registered substance (Amides, C18 unsaturated) was conducted applying the shake flask method. As final result is log Kow = 5.8, the HPLC method would have been more appropriated instead of the shake flask method.

 

The shake-flask method is based on the ratio of the two solubilities of the test substance in the pure solvents. The water solubility of the test material was measured as 1.6 ug/L in GLP study CH – 065/2010, but no data about n-octanol solubility was available even if, considering the molecular structure, a much higher solubility in n-octanol was expected.

 

Since the affinity for n-octanol of the test material is so much higher than for water, instrumental analysis was conducted only of the aqueous phases, assuming that the decrease in test item concentration in the n-octanolic phase is negligible.

 

The determination of the test material in the aqueous phase was performed by HPLC using the MS detector with the external standard method.

 

Full details of the experimental conditions are described in the robust study summary of the appropriate IUCLID sections.

 

The experiment was conducted in a GLP facilities, where all instruments are constantly calibrated and controlled. The GLP compliance of the lab is certified by the Italian Minister of Health.

 

The accuracy of the final result strongly depends on the accuracy and precision of the analytical balance that weighed the sample and the HPLC determination of the substance in the water phase. The analytical balance is fully compliant with the GLP requirements and constantly calibrated and controlled. They are calibrated once a year by external personnel using first class certified standards and once a week by internal personnel with second class certified standards. Also the HPLC determination can be considered reliable. The measure in the aqueous phase is determined directly, with neither further dilution nor extraction.

 

In the experimental section of the CH – 066/2010 study, the test material content in the n-octanolic phases can be considered precise as a consequence of the precision weight of the test material obtained with an analytical balance and due to the complete dissolution in the mother octanolic phase.

The test material content as measured in the aqueous phases can be considered precise by virtue of the direct injection into an HPLC Agilent mod. 1200 coupled with a Triple Quadrupole Mass Detector Agilent mod. 6410, without pre-treatment or extraction in order to avoid a possible lack of sample.

Moreover, the MRM technique permitted to avoid any interference as showed in the representative chromatograms presented in the Annex. The peak areas of the tested solutions are in the centre of the linearity range (1-10 ng/mL with a correlation factor of 0.99885).

 

It can be concluded that, even if the method seems not applicable and reliable for the substance, the result has been derived with good precision and it is consistent with the expected result

CONCLUSIONS

 

The accuracy of the result is supported by the consistency with the estimated value with QSAR evaluations and the results of HPLC measurements on very similar substances.

 

From a Risk Assessment point of view, the final result of Log Kow is >> 4 is triggering a concern for persistency and bioaccumulation. Therefore this issue has been taken into due account in the PBT and fate behaviour section and the less accurate measure is not affecting the final assessment. A more accurate measure would not change the final assessment.

 

The reference value taken into account for Risk Assessment is the calculated one on the pure substance(Log Kow 6.48), as the most conservative one.