Oligo

Partition coefficient

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

supporting study

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

Remarks:

The substance is not fully compliant with the applicability domain of the model. However, this calculation is used in a weight of evidence approach, in accordance to the REACh Regulation (EC) No 1907/2006, Annex XI General rules for adaptation of the standard testing regime set out in Annexes VII to X, 1.2. It is adequately documented and justified: the prediction is evaluated on the basis of the model performance on similar substances. For more details see section `overall remarks, attachments´.

Justification for type of information:

1. SOFTWARE
EPI Suite v4.11 Estimation Programs Interface Suite™ for Microsoft® Windows v 4.11. US EPA, United States Environmental Protection Agency, Washington, DC, USA.

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

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See “Test material information”

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached information on the model provided by the developer. Further information on the OECD criteria as outlined by the applicant is provided below under "Any other information of materials and methods incl. tables"

5. APPLICABILITY DOMAIN
See attached information and information as provided in "Overall remarks, attachments" section.

6. ADEQUACY OF THE RESULT
See assessment of adequacy as outlined in the "Overall remarks, attachments" section.

Qualifier:

according to guideline

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

- Software tool(s) used including version: EPI Suite v4.11
- Model(s) used: KOWWIN v1.68
The octanol-water partition coefficient of organic compounds is estimated starting from the chemical structure, which is divided into fragments (atom or larger functional groups). Coefficient values of each fragment or group are summed together to yield the log P estimate. For the complete method's description see field 'Any other information on materials and methods incl. tables'.
The datasets used for the model development (2447 molecules) and for the external validation (10946 molecules) are described in the field 'Any other information on materials and methods incl. tables'.
- Model description: see field 'Justification for type of information', 'Attached justification' and 'any other information on Material and methods'
- Justification of QSAR prediction: see field 'Justification for type of information', 'Attached justification' and/or 'overall remarks'

GLP compliance:

no

Type of method:

other: QSAR

Partition coefficient type:

octanol-water

Type:

log Pow

Partition coefficient:

3.4

Remarks on result:

other: QSAR result, no information on temperature and pH available.

Remarks:

Log Pow evaluated to the C16 Monoester constituents of the substance.

Type:

log Pow

Partition coefficient:

> 10

Remarks on result:

other: QSAR result, no information on temperature and pH available.

Remarks:

Log Pow estimated based on those calculated for the other constituents (always > 10).

KOWWIN Results for C16 Monoester constituent of the UVCB substance

 

Molecular weight of the evaluated structure: 580.72 (within the range of the model training set; 18.02-719.92)

 

Log Kow(version 1.68 estimate): 3.40

 

TYPE	MAX	NUM	LOGKOW FRAGMENT DESCRIPTION	COEFF	VALUE
Frag	13	1	-CH3 [aliphatic carbon]	0.5473	0.5473
Frag	18	17	-CH2- [aliphatic carbon]	0.4911	8.3487
Frag	16	8	-CH [aliphatic carbon]	0.3614	2.8912
Frag	3	1	C [aliphatic carbon – No H, not tert]	0.9723	0.9723
Frag	6	7 *	-OH [hydroxy, aliphatic attach]	-1.4086	-9.8602
Frag	5	3	-O- [oxygen, aliphatic attach]	-1.2566	-3.7698
Frag	3	1	-C(=O)O [ester, aliphatic attach]	-0.9505	-0.9505
Factor	3	2	C-O-C-O-C structure correction	0.5036	1.0072
Factor	1	1	Multi-alcohol correction	0.4064	0.4064
Factor	1	2 *	HO-CH-C(-O-)-CH-OH structure correction	1.0649	2.1298
Factor	2	1	HO-CH-C(-OH)-CH-OH structure correction	0.5944	0.5944
Factor	2	1	-O-C(-C-HO)-C-O- structure correction	0.85	0.85
Const			Equation Constant		0.229

* Fragments or factors exceeding the maximum number (MAX) present in the structures of the model’s training set.

 

 

KOWWIN Results for C18 Diester constituent of the UVCB substance

 

Molecular weight of the evaluated structure: 875.25 (outside the range of the model training set; 18.02-719.92)

 

Log Kow(version 1.68 estimate): 13.03

 

TYPE	MAX	NUM	LOGKOW FRAGMENT DESCRIPTION	COEFF	VALUE
Frag	13	2	-CH3 [aliphatic carbon]	0.5473	1.0946
Frag	18	35 *	-CH2- [aliphatic carbon]	0.4911	17.1885
Frag	16	8	-CH [aliphatic carbon]	0.3614	2.8912
Frag	3	1	C [aliphatic carbon – No H, not tert]	0.9723	0.9723
Frag	6	6	-OH [hydroxy, aliphatic attach]	-1.4086	-8.4516
Frag	5	3	-O- [oxygen, aliphatic attach]	-1.2566	-3.7698
Frag	3	2	-C(=O)O [ester, aliphatic attach]	-0.9505	-1.901
Factor	3	2	C-O-C-O-C structure correction	0.5036	1.0072
Factor	1	1	Multi-alcohol correction	0.4064	0.4064
Factor	1	1	HO-CH-C(-O-)-CH-OH structure correction	1.0649	1.0649
Factor	2	1	HO-CH-C(-OH)-CH-OH structure correction	0.5944	0.5944
Factor	2	2	-O-C(-C-HO)-C-O- structure correction	0.85	1.7
Const			Equation Constant		0.229

* Fragments or factors exceeding the maximum number (MAX) present in the structures of the model’s training set.

 

 

KOWWIN Results for C18 Pentaester constituent of the UVCB substance

 

Molecular weight of the evaluated structure: 1674.66 (outside the range of the model training set; 18.02-719.92)

 

Log Kow(version 1.68 estimate): 38.91

 

TYPE	MAX	NUM	LOGKOW FRAGMENT DESCRIPTION	COEFF	VALUE
Frag	13	5	-CH3 [aliphatic carbon]	0.5473	2.7365
Frag	18	83 *	-CH2- [aliphatic carbon]	0.4911	40.7613
Frag	16	8	-CH [aliphatic carbon]	0.3614	2.8912
Frag	3	1	C [aliphatic carbon – No H, not tert]	0.9723	0.9723
Frag	6	3	-OH [hydroxy, aliphatic attach]	-1.4086	-4.2258
Frag	5	3	-O- [oxygen, aliphatic attach]	-1.2566	-3.7698
Frag	3	5 *	-C(=O)O [ester, aliphatic attach]	-0.9505	-4.7525
Factor	3	2	C-O-C-O-C structure correction	0.5036	1.0072
Factor	1	1	Multi-alcohol correction	0.4064	0.4064
Factor	2	2	-O-C(-C-HO)-C-O- structure correction	0.85	1.7
Factor	1	1	C-O-C(-C-OH)-O-C correction	0.95	0.95
Const			Equation Constant		0.229

* Fragments or factors exceeding the maximum number (MAX) present in the structures of the model’s training set.

 

 

KOWWIN Results for C18 Octaester constituent of the UVCB substance

Based on the trend in the results obtained for the other constituents and the already high estimation obtained for C18 Pentaester, the evaluation of the Log Kow for this constituent was considered as not necessary.

Reference 2

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

other: EU Method A.8 - Appendix 1 (Partition Coefficient - Estimation method)

Qualifier:

according to guideline

Guideline:

other: OECD Test Guideline 105 Water Solubility

Qualifier:

according to guideline

Guideline:

other: ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7a: Endpoint specific guidance

Principles of method if other than guideline:

The partition coefficient of the test item was estimated by using the octanol solubility and the water solubility, according to EU Method A.8 - Appendix 1 and ECHA Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7a: Endpoint specific guidance (Version 6.0, 2017).

GLP compliance:

no

Type of method:

estimation method (solubility ratio)

Partition coefficient type:

octanol-water

Analytical method:

high-performance liquid chromatography

mass spectrometry

Type:

log Pow

Partition coefficient:

> 5.04

Temp.:

20 °C

Remarks on result:

other: pH not measured

Details on results:

The solubility of the test item in octanol was reported to be 55.6 g/L.
According to study report 85369 (section 4.8, Water solubility), the solubility in water is < 0.509 mg/L (below limit of quantification).

Based on these results, the log Pow can be estimated as follows (according to EU Method A.8, Appendix 1 – Estimation method):

Solubility in octanol (mg/L) = 55.6 * 1000 = 55600

Pow = 55600 / 0.509 = 109233.7917
log Pow = 5.04

As the water solubility is stated as < 0.509, the log Pow can be estimated as > 5.04.

Results

After the first incubation period at 30 °C overnight, particles of the test item remained. One bottle was transferred to the 20°C cabinet after 24 h incubation at 30 °C. The remaining two were transferred after at least 48 h and 72 h respectively. A mean solubility of 55.6 ± 5.93 g/L Octanol could be determined.

 

The following table summarizes the calculated results after LC measurements.

Measured Conc. (g/L Octanol)	Dilution factor	Calculated concentration (g/L Octanol)
1.17	40	46.9
1.28	40	51.1
1.38	40	55.3
1.41	40	56.4
1.54	40	61.5
1.56	40	62.3

 

Mean concentration: 55.6 g/L

Standard deviation: 5.93

RSD [%]: 10.66%

 

 

Conclusion

The Octanol solubility of the test item in Octanol is 55.6 ± 5.93 g/L.

Description of key information

Log Pow > 5.04 at 20 °C (EU Method A.8, appendix 1 - estimation method)

Additional information

The Log Pow was estimated using the octanol solubility (55.6 g/L, OECD Guideline 105, Flask Method) and the water solubility (< 0.509, OECD Guideline 105, Flask Method).

QSAR evaluation was performed to support the experimental results:

- A log Pow of 3.40 was obtained for the monoester constituent of the substance

- log Pow values always > 10 were obtained for all the other representative constituents (diester and pentaester)