2H-Pyran, tetrahydro-3-(phenylmethyl)-

Partition coefficient

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Test dates: April 22 to August 24, 2005

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The study was conducted according to an internationally recognised method, and under GLP. Deviation in test conditions may affect the accuracy. The substance is considered to be adequately characterised. Therefore validation applies with restrictions.

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient - Shake Flask Method)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)

GLP compliance:

yes (incl. QA statement)

Remarks:

effective 27/09/2004

Type of method:

flask method

Partition coefficient type:

octanol-water

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature protected from direct sunlight.

Analytical method:

gas chromatography

Key result

Type:

log Pow

Partition coefficient:

3

Temp.:

20 °C

pH:

ca. 0 - ca. 14

ratio	ratio 1:10		ratio 2:10		ratio 1:20
replicate vessel	1	2	1	2	1	2
log Kow	2,95	2,93	3,00	2,99	2,98	2,97
mass balance	94,0%	97,6%	97,3%	93,0%	93,1%	91,4%

Mean log Pow and SD = 2.97 +/-0.03

The observed interval within the six log Pow values was [2.93 - 3.00] and the validity criteria was fulfilled (< +/-0.3 unit).

The pH of the water phase was not measured.

Conclusions:

The substance has low potential to bioaccumulate in the environment, according to CLP classification criteria for aquatic chronic toxicity (log Kow <4).

Executive summary:

The partition coefficient of the test substance was determined under GLP according to EU A.8 guideline, flask method.

Determinations were conducted in duplicate for three solvents ratio, concentrations were measured using a GC-FID validated method. Individual results fulfilled the validity criteria for reproducibility, and mass balance was satisfactory, so the average value is retained.

The log Kow has been determined to be 3.0 at 20°C.

Reference 2

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Study period:

March 21st, 2018

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. SOFTWARE
iSafeRat® toolbox – in Silico Algorithms For Environmental Risk And Toxicity version 2.4

2. MODEL (incl. version number)
iSafeRat® holistic HA-QSAR v1.8

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
c1ccccc1CC2COCCC2

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF.

5. APPLICABILITY DOMAIN
See attached QPRF.

6. ADEQUACY OF THE RESULT
See attached QPRF.

Qualifier:

equivalent or similar to guideline

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 purpose of the in silico study was to determine the log Kow of the test item. The determination was performed using a core-centred substitution method (C2SM) in which the molecule is divided into a core and substituents and each fragment is related to a specific contribution of log Kow which may be positive or negative. The final log Kow is determined by simple addition of the fragments. The predicted log Kow values have been validated against high quality experimental studies generally using the shake-flask method but slow-stir values have been used when available. The results are considered to be as accurate as those from a good quality OECD 107 or 123 study.

GLP compliance:

no

Type of method:

calculation method (fragments)

Partition coefficient type:

octanol-water

Specific details on test material used for the study:

Not applicable

Type:

log Pow

Partition coefficient:

2.6

Temp.:

25 °C

Details on results:

All the required fragment contribution values were available from the iSafeRat® log Kow module. Since no missing fragments were identified, the 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: benzene x 1
• heptyl x 1
• ring closure x 1
• ether x 1

All the necessary fragment contribution values were available from the iSafeRat® log KOW module or derived from the data of the literature. As each contribution value was derived based on high quality data, the derived log Kow for the test item is considered to be highly accurate. Due to the nature of the modelisation method (substitution-based approach) to the best of our knowledge there is no method to quantify the uncertainty of the prediction. The predictivity of the model has been evaluated by external validation to have a RMSEP of 0.1816 (RMSEP closer to zero indicated that the model is associated with a reliable predictivity).

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 n-octanol/water partition coefficient of the test item. This QSPR model has been validated as a QSAR model to be compliant with the OECD recommendations for QSAR modeling (OECD, 2004) and 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" and No. 123 "Partition Coeficient (n-octanol/water): Slow Stirring Method”. The criterion predicted was the log Kow (also known as log Pow).

The determination was performed using a core-centred substitution method (C2SM) in which the molecule is divided into a core and substituents, and each fragment is related to a specific contribution of log Kow which may be positive or negative. The final log Kow is determined by simple addition of the fragments. The predicted log Kow values have been validated against high quality experimental studies generally using the shake-flask method but slow-stir values have been used when available. The results are considered to be as accurate as those from a good quality OECD 107 or 123 study.

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 calculated log Kow value is predicted as 2.6 at 25°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 (log Kow<4).

Key value for chemical safety assessment

Log Kow (Log Pow):

3

at the temperature of:

20 °C

Additional information

A reliable experimental study, conducted according to a recognized EC method and under GLP, is available. However, it shows some restrictions due to deviation in test conditions.

Therefore, a QSAR calculation, valid as falling into the applicability domain, was added for comparison purpose.

Both results were consistent (exp. 2.97 vs calc. 2.6), which confirms the validity of the experimental test. So, it is considered as the key study, and the result is retained as key data, while the QSAR is considered as a supporting information.

The accuracy of the experimental value was further confirmed in the holistic approach used to calculate the water solubility of the substance; please refer to IU section 4.8.