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Partition coefficient

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Endpoint:
partition coefficient
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
2017-02-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
1. SOFTWAREiSafeRat® toolbox – in Silico Algorithms For Environmental Risk And Toxicity version 2.22. MODEL (incl. version number)iSafeRat® holistic HA-QSAR v1.63. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODELC1C(CCC)COC(=O)C14. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL See attached QMRF5. APPLICABILITY DOMAINSee attached QPRF:6. ADEQUACY OF THE RESULT See attached QPRF
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)
Deviations:
not applicable
Remarks:
QSAR model
Principles of method if other than guideline:
The determination was performed using a fragment based approach in which the molecule is divided into large and small fragments and each fragment is related to a specific log KOW contribution which may be positive or negative. The final log KOW is determined by simple addition of the fragments.
GLP compliance:
no
Type of method:
calculation method (fragments)
Remarks:
QSAR
Partition coefficient type:
octanol-water
Key result
Type:
log Pow
Partition coefficient:
1.3
Temp.:
25 °C
Remarks on result:
other: pH not applicable to QSAR
Remarks:
from structure, no pH dependency anticipated
Details on results:
All the required fragment contribution values were available from the iSafeRat® log KOW module. Since no missing fragments were identified, test item is within the structural fragment domain of the model. The fragments (and number of occurrences) used for the calculation are as following:· core: cyclononane x1· Propyl x1· Lactone x1 All the necessary fragment contribution values were available from the iSafeRat® log KOW module. As each contribution value was derived based on high quality data, the derived log KOW for test item was considered to be highly accurate.

no data

Conclusions:
Low potential for bioaccumulation, based on CLP criteria for Aquatic Chronic toxicity (log Kow<4).
Executive summary:

A Quantitative Structure-Property Relationship (QSPR) model was used to calculate the log Kow of the test item. This calculation method predicts the endpoint value which would be expected when testing the substance under experimental conditions in a laboratory following the Guideline for Testing of Chemicals No. 107, "Partition Coeficient (n-octanol/water): Shake Flask Method" (2) and No. 123 "Partition Coeficient (n-octanol/water): Slow Stirring Method” (3). The criterion predicted was the log KOW (also known as log POW).

The determination was performed using a fragment based approach in which the molecule is divided into large and small fragments and each fragment is related to a specific log KOW contribution which may be positive or negative. The final log KOW is determined by simple addition of the fragments.

The test item falls within the applicability domain of the model and was therefore reliably predicted for its log KOW.

Based on the structure, the log KOW is predicted as follows: 1.3 at 25°C.

Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
other information
Study period:
03-25 April 2006
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
unsuitable test system
Remarks:
The study was conducted according to an internationally recognised method, and under GLP. However, surface-active behaviour is suspected. Therefore validation cannot be granted.
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
EU Method A.8 (Partition Coefficient - Shake Flask Method)
GLP compliance:
yes (incl. certificate)
Remarks:
signed 24 February 2006
Type of method:
flask method
Partition coefficient type:
octanol-water
Analytical method:
gas chromatography
Type:
log Pow
Partition coefficient:
1.37
Temp.:
20 °C

In a first experiment, 40 mL of pre-saturated water were mixed with 4 mL of the 10 g/L stock solution. The tubes were centrifuged for 10 min at 5000 rpm and 20°C.

Concentrations as high as 120 mg/L were measured in the water phase, which exceed the measured hydrosolubility, and the results were not retained. The hypothesis was that the system was saturated with test item, and hat micro-drops still remain in the water phase.

In a second experiment, 40 mL of pre-saturated water were mixed with 4 mL of pre-saturated n-octanol and 0.4 mL of the 10 g/L solution. The tubes were centrifuged 10 min at 5000 rpm and 20°C.

Here also the water concentrations exceeded the water hydrosolubility, and the results were not retained.

The third experiment was performed using 40 mL of pre-saturated water, 4 mL of pre-saturated n-octanol and 40 µL of the 10 g/L stock solution.

In this case, the water concentrations complied with the value of hydrosolubility ans the test was reproduced using half and twice, respectively, the above volume ratio.

  n-octanol:water ratio 1:10 ratio 2:10 ratio 1:20
  replicate vessel 1 2 1 2 1 2
volumes (mL) n-octanol 4,0 4,0 8,0 8,0 2,0 2,0
  water 40,0 40,0 40,0 40,0 40,0 40,0
  stock solution 0,04 0,04 0,08 0,08 0,02 0,02
nominal amount (mg)   0,40 0,40 0,80 0,80 0,20 0,20
conc. in octanol (mg/L)   68,1 67,6 80,8 81,1 53,9 54,9
conc. in water (mg/L)   2,6 2,6 4,2 4,2 2,2 2,2
log Kow   1,42 1,41 1,28 1,29 1,39 1,40
measured amounts (mg)              
  in n-octanol 0,275 0,273 0,653 0,655 0,109 0,111
  in water 0,103 0,105 0,169 0,167 0,088 0,087
  total 0,378 0,378 0,822 0,822 0,197 0,198
recovery (%)   93,8 93,8 101,9 101,9 97,4 98,2
Executive summary:

The partition coefficient of the test substance was determined under GLP according to EU A.8 guideline, flask method. In the first two series, concentrations in the water phase were found above the solubility, suggesting surface-active potential. The third run, conducted at lower concentrations, fulfilled the validity criteria, and the average value was retained.

The log Kow has been determined to be 1.37 at 20°C.

Description of key information

The data is relevant for classification in aquatic chronic toxicity hazard class, according to CLP criteria.

The substance has low potential for bioaccumulation (calculated log Kow<4).

Key value for chemical safety assessment

Log Kow (Log Pow):
1.3
at the temperature of:
25 °C

Additional information

An experimental study, conducted according to a recognized EC method and under GLP, is available. However, preliminary testing and inconsistency with experimental water solubility suggest that the substance may exhibit surface-activity, despite the structural formula shows no alert. The final test fulfilled the validity criteria, but reliability cannot be granted.

Therefore, a calculation from a fully valid QSAR was additionally performed. The result (logKow = 1.3) was found to be consistent with the experimental value (1.37).

Due to experimental issues, the calculated value was prefered, and retained as key data.