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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:
25 October 2016
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
QSAR prediction
Guideline:
other: REACH guidance on QSARs R.6.
Principles of method if other than guideline:
KOWWIN™ Program (v1.68) (executed by EPI Suite in QSAR Toolbox 3.4.0.17). Estimates the log octanol-water partition coefficient, log KOW, of chemicals using an atom/fragment contribution method.
GLP compliance:
no
Remarks:
Not applicable to QSAR models
Type of method:
other: QSAR
Partition coefficient type:
octanol-water
Key result
Type:
log Pow
Partition coefficient:
ca. 7.8
Remarks on result:
not measured/tested
Remarks:
QSAR
Details on results:
KOWWIN (v1.68) computer program excuted by EPI Suite v4.10 was used to estimate Log Kow.

The Log Kow for the major component was estimated to be 7.8 .
Conclusions:
The estimated values by KOWWIN for the major component for the Substance was 7.8.
Executive summary:

The substance is considered to be a UVCB (Chemical Substances of Unknown or Variable Composition, Complex Reaction Products and Biological Materials). The complex nature and physical properties of the Substance resulted in 2 peaks in the Octanol/Water Partition Coefficient study. In this study HPLC-UV detection was used however it was noted that use of UV detection is limited to those components of UVCB materials with chromophoric functionality. The major component is considered to have no significant UV-Vis absorbing functionality. Other detectors may have provided a different set of responses, however, in the opinion of the Study Director, the experimental design and conditions presented in this study were deemed to be most appropriate for the estimation of Log POW for this test substance.

 

The complex nature and physical properties of the substance made it difficult to provide a suitable log Kow value. Consequently, QSAR was used to provide clarity and reflect the representative chemistry of the Substance model is a US EPA accepted QSAR method for organic chemicals properties assessment. The estimated values by KOWWIN for the major component for the Substance was 7.8.

Endpoint:
partition coefficient
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
25 October 2016
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
QSAR prediction
Guideline:
other: REACH guidance on QSARs R.6.
Principles of method if other than guideline:
Log P Model (MULTICASE Inc) in QSAR Toolbox 3.4.0.17. Estimates the log octanol-water partition coefficient, log KOW, of chemicals.
GLP compliance:
no
Remarks:
Not applicable to QSAR models
Type of method:
other: QSAR
Partition coefficient type:
octanol-water
Specific details on test material used for the study:
The use of a QSAR model was used to clarify the partition coeffecient of the Substance and ensure that the value is reflects the major component for that Substance.

Log Kow values were estimated using og P Model (MULTICASE Inc) in QSAR Toolbox 3.4.0.17. The LogP program estimates the log octanol/water partition coefficient (log P) of organic chemicals.
Key result
Type:
log Pow
Partition coefficient:
ca. 8.34
Remarks on result:
not measured/tested
Remarks:
QSAR
Details on results:
Log P Model (MULTICASE Inc) in QSAR Toolbox 3.4.0.17 was used to estimate Log Kow.

The Log Kow for the major component was estimated to be 8.34 .
Conclusions:
The estimated values by log P Model (MULTICASE Inc) in QSAR Toolbox 3.4.0.17 for the major component for the Substance was 8.34.
Executive summary:

The substance is considered to be a UVCB (Chemical Substances of Unknown or Variable Composition, Complex Reaction Products and Biological Materials). The complex nature and physical properties of the Substance resulted in 2 peaks in the Octanol/Water Partition Coefficient study. In this study HPLC-UV detection was used however it was noted that use of UV detection is limited to those components of UVCB materials with chromophoric functionality. The major component is considered to have no significant UV-Vis absorbing functionality. Other detectors may have provided a different set of responses, however, in the opinion of the Study Director, the experimental design and conditions presented in this study were deemed to be most appropriate for the estimation of Log POW for this test substance.

 

The complex nature and physical properties of the substance made it difficult to provide a suitable log Kow value. Consequently, QSAR was used to provide clarity and reflect the representative chemistry of the Substance model is a US EPA accepted QSAR method for organic chemicals properties assessment. The estimated values by log P Model (MULTICASE Inc) in QSAR Toolbox 3.4.0.17 for the major component for the Substance was 8.34.

Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
EPA OPPTS 830.7570 (Partition Coefficient, n-octanol / H2O, Estimation by Liquid Chromatography)
Qualifier:
according to
Guideline:
OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)
Qualifier:
according to
Guideline:
EU Method A.8 (Partition Coefficient)
GLP compliance:
yes
Type of method:
HPLC method
Partition coefficient type:
octanol-water
Analytical method:
high-performance liquid chromatography
Key result
Type:
log Pow
Partition coefficient:
> 6.5
Temp.:
40 °C
pH:
6
Remarks on result:
not determinable because of methodological limitations
Type:
log Pow
Partition coefficient:
> 1.078 - <= 1.082
Temp.:
40 °C
pH:
6
Remarks on result:
other: Peak 1
Details on results:
The three aliquots of the 100 mg/L EXP1505385 solution were sequentially injected. The EXP1505385 test substance reproducibly eluted as two peaks on the UV detector. The capacity factor (k) for each peak was calculated based on the corresponding retention times and the results for the three injections were averaged. The corresponding estimated mean Log POW for the two test substance peaks was calculated to be 1.08 and >6.50, respectively. The calculated mean retention times, capacity factors, and mean n octanol/water partition coefficients for EXP1505385 are presented in Table 5.

Table 5

 

Logn-Octanol/Water Partition Coefficients (Log POW) Based on UV Data for EXP1505385

 

Sample

Number

(523C-207,218-)

Retention

Time

(minutes)

Mean ()

Standard

Deviation (SD)1

Capacity

Factor (k)1,2

Mean ()

Standard

Deviation (SD)1

Log k1

POW1

Log POW1

Mean ()

Standard

Deviation (SD)1

12639 (Injection 1) (Peak 1)

12639 (Injection 2) (Peak 1)

12639 (Injection 3) (Peak 1)

1.847

1.848

1.847

= 1.847

SD = 0.00058

0.245

0.246

0.245

= 0.246

SD = 0.00039

-0.610

-0.609

-0.610

11.9

12.0

11.9

1.07

1.08

1.07

= 1.08

SD = 0.0023

12639 (Injection 1) (Peak 2)

12639 (Injection 2) (Peak 2)

12639 (Injection 3) (Peak 2)

24.796

24.803

24.806

= 24.802

SD = 0.0051

15.7

15.7

15.7

= 15.7

SD = 0.0035

1.20

1.20

1.20

>3,162,278

>3,162,278

>3,162,278

>6.50

>6.50

>6.50

= >6.50

SD = N/A

N/A = Not Applicable

1  Values obtained utilizing Microsoft®Excel 2010 in full precision mode. Manual calculations may differ slightly.

2  Capacity factor (k) is the sample retention time minus the mean column dead time (1.483 minutes for thiourea) divided by the mean column dead time.

Conclusions:
Under the chromatographic conditions specified, the Substance eluted as two discrete peaks, corresponding to mean estimated log POW values of 1.08 and >6.50.
Executive summary:

The test was performedbased on procedures in the U.S. EPA Product Properties Test Guidelines, OPPTS 830.7570,Partition Coefficient (n-Octanol/Water), Estimation by Liquid Chromatography(1); OECD Guideline for Testing of Chemicals, 117,Partition Coefficient (n-octanol/water), High Performance Liquid Chromatography (HPLC) Method(2); Official Journal of the European Communities No. L383. Method A.8: Partition Coefficient(3) and TSCA Title 40 of the Federal Code of Regulations, Part 796, Section 1570: Partition Coefficient (n-Octanol/Water) – Estimation by Liquid Chromatography(4).

Under the chromatographic conditions specified, EXP1505385 eluted as two discrete peaks. The mean log POWfor each of the peaks is presented in the following table:

 

Peak Number

Mean Log Pow

1

1.08 ± 0.0023

2

>6.50


Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18 April 20001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)
GLP compliance:
yes
Type of method:
HPLC method
Partition coefficient type:
octanol-water
Analytical method:
high-performance liquid chromatography
Key result
Type:
log Pow
Partition coefficient:
> 6.25
Temp.:
24 °C
Remarks on result:
not determinable because of methodological limitations
Details on results:
The test substance eluted as one component group at a retention time greater than the latest eluting reference compound 4,4'-DDT. Therefore, the Log Pow value is estimated to be >6.20.

see attached background document

Conclusions:
The test substance eluted as one component group at a retention time greater than the latest eluting reference compound 4,4'-DDT. Therefore, the Log Pow value is estimated to be >6.20..
Executive summary:

The n-octanol/water partition coefficient (Pow) of the test substance was estimated by reverse phase high performance liquid chromatography (HPLC). This procedure was based on the methods outlined in the OECD Guideline for Testing of Chemicals 117: "Partition Coefficient (n-OctanollWater), High Performance Liquid Chromatography (HPLC) Method" and EC Annex V, Method A.8 "Partition Coefficient".

For certain small organic molecules in their non-ionized form, a relationship has been demonstrated in which the Log Powcorrelates with the compound's potential to transfer from water into organic matter. As a result, Log Powhas become established as an accepted measure of a compound's potential to partition into organic material regardless of its chemical class. The HPLC method exploits the relationship between the Log Pow values of pure organic compounds and their retention times (expressed as capacity factors, k) in a reverse phase liquid chromatography system to estimate the Powof organic substances.

The test substance eluted as one component group at a retention time greater than the highest reference compound when analyzed by HPLC. The estimated Log Powvalues for the test substance is >6.2.

Description of key information

Two studies were conducted and estimated that the Substance will have Partition coefficient greater than the highest reference material (DDT, log Kow = 6.2 to 6.5). Values have also been estimated from KOWWIN (EpiSuite 4.10)and Log P(Multicase inc)QSAR models in the QSAR Toolbox 3.4.0.17. Log Kow estimated values for Substance using these models are 7.8 - 8.34. Therefore this confirms that the Substance is likely to have a log Kow >6.2

Key value for chemical safety assessment

Additional information

Initial attempts were made to experimentally determine the Partition Coefficient (Kow) for registration of the Substance. The Substance is considered to be a UVCB (Chemical Substances of Unknown or Variable Composition, Complex Reaction Products and Biological Materials). The complex nature and physical properties of the Substance resulted in 2 peaks in the Octanol/Water Partition Coefficient study. In this study HPLC-UV detection was used however it was noted that use of UV detection is limited to those components of UVCB materials with chromophoric functionality. The major component is considered to have no significant UV-Vis absorbing functionality. Other detectors may have provided a different set of responses, however, in the opinion of the Study Director, the experimental design and conditions presented in this study were deemed to be most appropriate for the estimation of Log POW for this test substance.  

The complex nature and physical properties of the substance made it difficult to provide a suitable log Kow value. Consequently, QSAR models was used to provide clarity and reflect the representative chemistry of the Substance. This was executed using KOWWIN (EpiSuite) and Log P (Multicase inc) model in the QSAR Toolbox 3.4.0.17. The weight of evidence estimated the Log Kow for the representative Substance is >6.2.