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Physical & Chemical properties

Partition coefficient

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Endpoint:
partition coefficient
Type of information:
other: QSAR and experimental data
Adequacy of study:
key study
Study period:
2017-06-25 to 2017-06-26
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: results from QSAR model and literature data
Justification for type of information:
1. SOFTWARE
iSafeRat® toolbox – in Silico Algorithms For Environmental Risk And Toxicity version 2.3

2. MODEL (incl. version number)
iSafeRat® holistic HA-QSAR v1.7

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
α-pinene CC1=CCC2CC1C2(C)C
α-phellandrene CC1=CCC(C=C1)C(C)C
limonene CC1=CCC(CC1)C(=C)C
p-cymene CC1=CC=C(C=C1)C(C)C
β-phellandrene CC(C)C1CCC(=C)C=C1
carene (Δ3) CC1=CCC2C(C1)C2(C)C
germacrene D CC1=CCCC(=C)C=CC(CC1)C(C)C
germacrene D 1,10-epoxide C=C1C=CC(C(C)C)CCC2(C)OC2CC1
sabinene CC(C)C12CCC(=C)C1C2
β-pinene CC1(C2CCC(=C)C1C2)C
spathulenol CC1(C2C1C3C(CCC3(C)O)C(=C)CC2)C
elemol CC(=C)C1CC(CCC1(C)C=C)C(C)(C)O
myrcene CC(=CCCC(=C)C=C)C
β-caryophyllene CC1=CCCC(=C)C2CC(C2CC1)(C)C

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 consituents of the test item Essential oil of Schinus Terebinthifolius (Anacardiaceae) obtained from red berries by supercritical carbon dioxide extraction. 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 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. Some log KOW values are coming from literature.
GLP compliance:
no
Type of method:
calculation method (fragments)
Partition coefficient type:
octanol-water
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: confidential data
- Expiration date of the lot/batch: confidential data
- Purity test date: confidential data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: confidential data
- Stability under test conditions: confidential data
- Solubility and stability of the test substance in the solvent/vehicle: confidential data
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: confidential data
Type:
log Pow
Partition coefficient:
4.46
Temp.:
20 °C
Remarks on result:
other: alpha-pinene
Type:
log Pow
Partition coefficient:
4.6
Temp.:
25 °C
Remarks on result:
other: alpha-phellandrene
Type:
log Pow
Partition coefficient:
4.57
Temp.:
25 °C
Remarks on result:
other: limonene
Type:
log Pow
Partition coefficient:
4.1
Temp.:
25 °C
Remarks on result:
other: p-cymene
Type:
log Pow
Partition coefficient:
4.3
Temp.:
25 °C
Remarks on result:
other: b-phellandrene
Type:
log Pow
Partition coefficient:
4.38
Temp.:
37 °C
Remarks on result:
other: carene (Δ3)
Type:
log Pow
Partition coefficient:
6.4
Temp.:
25 °C
Remarks on result:
other: germacrene D
Type:
log Pow
Partition coefficient:
4.4
Temp.:
25 °C
Remarks on result:
other: sabinene
Type:
log Pow
Partition coefficient:
4.425
Temp.:
25 °C
Remarks on result:
other: b-pinene
Type:
log Pow
Partition coefficient:
3.68
Temp.:
22.5 °C
Remarks on result:
other: elemol
Type:
log Pow
Partition coefficient:
4.82
Temp.:
30
pH:
6.5
Remarks on result:
other: myrcene
Type:
log Pow
Partition coefficient:
6.4
Temp.:
25 °C
Remarks on result:
other: β-caryophyllene
Type:
log Pow
Partition coefficient:
6.3
Temp.:
25 °C
Remarks on result:
other: bicyclogermacrene
Details on results:
These values have been obtained using QSAR model and litterature data. For the calculated values, in silico studies have been provided as supporting study in this dossier.

Data source

Constituents

log KOWat 25°C

source

α-pinene

4.46

https://echa.europa.eu/fr/brief-profile/-/briefprofile/100.001.175, brief profile - Last updated: 11/07/2017

α-phellandrene

4.6

KREATiS (2017) Calculated value using iSafeRat® High-Accuracy QSAR model

limonene

4.57

[Li J, Perdue EM; Physicochemical properties of selected monoterpenes. Preprints of papers presented at the 209th ACS National Meeting Anaheim, CA April 2-7, 35(1): 134-7 (1995)] (data consulted on HSDB)

p-cymene

4.10

KREATiS (2017) Calculated value using iSafeRat® High-Accuracy QSAR model

β-phellandrene

4.3

KREATiS (2017) Calculated value using iSafeRat® High-Accuracy QSAR model

carene (Δ3)

4.38

https://echa.europa.eu/fr/brief-profile/-/briefprofile/100.033.367, brief profile - Last updated: 06/07/2017

germacrene D

6.4

KREATiS (2017) Calculated value using iSafeRat® High-Accuracy QSAR model

sabinene

4.4

KREATiS (2017) Calculated value using iSafeRat® High-Accuracy QSAR model

β-pinene

4.425

https://echa.europa.eu/fr/brief-profile/-/briefprofile/100.038.222, brief profile - Last updated: 17/07/2017

elemol

3.68

https://echa.europa.eu/fr/brief-profile/-/briefprofile/100.041.660, brief profile - Last updated: 06/07/2017

myrcene

4.82

https://echa.europa.eu/fr/brief-profile/-/briefprofile/100.004.203, brief profile - Last updated: 11/07/2017

β-caryophyllene

6.4

KREATiS (2017) Calculated value using iSafeRat® High-Accuracy QSAR model

 bicyclogermacrene  6.3   

KREATiS (2017) Calculated value using iSafeRat® High-Accuracy QSAR model

Conclusions:
Individual log Kow of major constituents > 4 (at 25°C).
The substance has potential for bioaccumulation, according to CLP classification criteria for aquatic chronic toxicity.
Executive summary:

The partition coefficient of the test item was derived from the range of the individual log Kow values of 13 constituents, representing 93% of a typical composition.

Some data was found in literature sources and considered as reliable.

When not available, a Quantitative Structure-Property Relationship (QSPR) model was used. The determination was performed using a fragment-based approach. All of the constituents fall within the applicability domain of the model and were therefore reliably predicted for their log Kow.

The partition coefficient of the constituents were found in the range 3.68 to 6.4, only one minor was <4.

Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
experimental dates: August 12-27, 2008
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The study was conducted according to an internationally recognized method, and under GLP, but with minor restrictions on accuracy (calibration, extrapolation). Test substance is adequately specified.
Qualifier:
according to guideline
Guideline:
OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)
Version / remarks:
April 13,2004
Qualifier:
according to guideline
Guideline:
EU Method A.8 (Partition Coefficient - HPLC Method)
Version / remarks:
EEC Directive 92/69, L383A, December 1992.
GLP compliance:
yes (incl. QA statement)
Remarks:
signed on 2008-11-12
Type of method:
HPLC method
Partition coefficient type:
octanol-water
Analytical method:
high-performance liquid chromatography
Type:
log Pow
Partition coefficient:
>= 2.63 - <= 6.13
Temp.:
25 °C
pH:
5
Type:
log Pow
Partition coefficient:
>= 7.52 - <= 7.64
Temp.:
25 °C
pH:
5

Calibration

Linear Regression:

slope = 0.297

y-axis intercept = -0.762

coefficient of regression (r) = 0.992

Results

For the test item, two series of peaks were observed.

For the 1st series, a log Kow range was determined from the 1st and last peak. For the 2nd series, 2 major peaks were identified, and their log Kow was extrapolated from the regression.

Conclusions:
Some constituents of the test substance have potential to bioaccumulate in the environment, according to CLP classification criteria for aquatic chronic toxicity (log Kow >4).
Executive summary:

A preliminary estimation from ratio of individual solubility in octanol and water gave a logKow > 5.6.

Then, the partition coefficient of the test substance was determined according to OECD 117 guideline, HPLC method, under GLP.

The system was calibrated with 6 reference substances, with logKow ranging between 1.0 and 6.5, giving good linear regression.

Then the test substance was injected in triplicate, and the partition coefficient was derived from the calibration curve.

Two series of peaks were observed, corresponding to log Kow in the ranges 2.63 - 6.13 and 7.52 - 7.64, at 25°C and pH=5.0.

Description of key information

Individual log Kow of major constituents > 4 (at 25°C).

The substance has potential for bioaccumulation, according to CLP classification criteria for aquatic chronic toxicity.

Key value for chemical safety assessment

Additional information

The individual values of 13 major constituents, representing 93% of a typical composition, were gathered from reliable literature sources, or estimated by QSAR when not publicly available. The result is expressed as a range, no key value was determined.

A supporting HPLC study confirms constituents with logKow ranging between ca 2.6 and 7.6, therefore potentially >4 too.