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Partition coefficient

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Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Experimental Dates (main test): February 25-26, 2020
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The study was conducted according to an internationally recognised method, with no deviation, and under GLP. The substance is adequately characterised, with isomers composition. Therefore full validation applies.
Qualifier:
according to guideline
Guideline:
OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)
Version / remarks:
13 April 2004
Qualifier:
according to guideline
Guideline:
other: EU Method A.24: “Partition coefficient (n-octanol/water), High Performance Liquid Chromatography (HPLC) method”
Version / remarks:
2016
GLP compliance:
yes (incl. QA statement)
Remarks:
signed on 15 Nov. 2018
Type of method:
HPLC method
Partition coefficient type:
octanol-water
Analytical method:
high-performance liquid chromatography
Key result
Type:
log Pow
Partition coefficient:
>= 4.76 - <= 4.94
Temp.:
30 °C
pH:
ca. 5

Preliminary test

A linear regression of log k versus log Pow for the reference items was carried out and the following equation was obtained:

log k = 0.2414 log Pow - 0.4406

with R = 0.9916 and R² = 0.9834.

For the test item, two peaks were observed with retention times of 17.53 min and 19.19 min. The dead time t0, determined with the peak of formamide, was 2.91 min.

The log Pow values corresponding to the two peaks of the test item were then deduced from the previous equation:

Peak 1: log Pow = 4.72;

Peak 2: log Pow = 4.93.

The coefficient of determination obtained with the reference solutions is higher than 0.95 and the retention times of the test item are included in the range of the retention times of the reference items. Therefore, these reference items will be used for the main test.

Main test

Reference items

 Compound  log Pow  log k (mean)
 ethylbenzene  3.2  0.32
 cumene  3.7  0.45
 biphenyl  4.0  0.51
 phenanthrene  4.5  0.71
 butylbenzene  4.6  0.69
 2,6-diphenylpyridine  4.9  0.75
 triphenylamine  5.7  0.98
 DDT  6.5  1.09

The formamide, used for the determination of the dead time, had a retention time of 2.91 minutes in the first injection of the reference items mix and of 2.92 in the second injection of the reference items mix.

The logarithms of the mean capacity factors, log k, are plotted as a function of the logarithms of the partition coefficient, log Pow.

The determination coefficient R2 observed is 0.9835 and the correlation coefficient R is 0.9917. The equation of the line issued from this linear regression will be used for the test item log Pow calculation: y = 0.2411x - 0.4304

Test item

A typical chromatogram of the test item is constituted of four peaks.

   mean tR  area (%)  mean logPow (SD, n=3)
 Dead time t0  2.92    
 Peak 1  18.07  47.4%  4.76 (0.023)
 Peak 2  19.77  43.4%  4.94 (0.000)
 Peak 3  20.59  5.5%  5.02 (0.000)
 Peak 4  22.45  3.7%  5.20 (0.023)

Since the test item is not a group of homologues, the weighted average log Pow is not calculated.

The pH value measured in the ultrapure water used for the mobile phase was 5.

The temperature variations of the oven containing the HPLC column were included in the range 29.5 °C - 30.3 °C.

Conclusions:
The constituents have potential for bioaccumulation, 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 OECD 117/EU A24 guideline, using the HPLC method.

The system was calibrated with eight reference substances, with logPow ranging between 3.2 and 6.5. The test item elutes in four peaks, with two very major (>40% area each), assumed to be related to the two defined constituents.

The corresponding logPow are respectively 4.76 and 4.94 (at pH 5 and 30°C).

Endpoint:
partition coefficient
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Study period:
run on 2019-08-08
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source
Justification for type of information:
1. SOFTWARE
EPI Suite (US EPA)

2. MODEL (incl. version number)
KOWWIN v1.68 (September 2010)

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
OCC(=CCCC(C(C1C2)(C1C3)C)(C23)C)C

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
generally acknowledged source

5. APPLICABILITY DOMAIN
The model is considered suitable as all fragments are described and for MW < 1000 g/mol.

6. ADEQUACY OF THE RESULT
The estimation is provided to assess bioaccumulation potential, based on CLP classification criteria for aquatic chronic toxicity (log Kow <4 or >4).
Principles of method if other than guideline:
QSAR calculation
GLP compliance:
no
Type of method:
calculation method (fragments)
Partition coefficient type:
octanol-water
Type:
log Pow
Partition coefficient:
4.96
Remarks on result:
other: Temp and pH not specified, assumed ambient T and non-ionised form

Calculated from fragments: Log Kow (estimate) = 4.9623

Conclusions:
The constituent has potential for bioaccumulation, according to CLP classification criteria for aquatic chronic toxicity (log Kow >4).
Executive summary:

The partition coefficient of the constituent was modelled with the KowWin estimation tool, which is part

of the US EPA Episuite modelling tool box.

The substance was characterised with its SMILES code.

The calculated logKow is 4.96.

Description of key information

With the two major constituents having logKow of 4.76 and 4.94, the substance has potential for bioaccumulation, according to CLP classification criteria for aquatic chronic toxicity (log Kow >4).

It should also be of concern for PBT assessment (logKow >4.5).

Key value for chemical safety assessment

Additional information

A new, fully reliable, experimental study was conducted on the registered substance. Therefore it is considered as the key data. Four constituents were detected, with measured logKow between 4.76 and 5.20.


No single key value was derived for the multi-constituent substance, result expressed as a range was prefered, having more scientific sense. According to the substance definition, only the two major constituents were considered; the other two are assumed to be impurities.


These results are consistent with predictions calculated for the analogue and major constituent alpha-Santalol, with EpiSuite QSAR model: 4.96.