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Physical & Chemical properties

Partition coefficient

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Administrative data

Endpoint:
partition coefficient
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
2019-11-21
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:
In general it should be noted ahead that this type of information is provided due to the last changes in the IUCLID software. According to REACH, if the test cannot be performed (e.g. the substance decomposes, has a high surface activity, reacts violently during the performance of the test or does not dissolve in water or in octanol, or it is not possible to obtain a sufficiently pure substance), a calculated value for log P as well as details of the calculation method shall be provided. The substance is an UVCB substance with a large variety of organic substances and biological materials, which cannot be totally transferred into a SMILES code, which is a prerequisite for QSAR estimations. E.g. proteins and fibres cannot be transformed here in a SMILES code. So in order to fulfil the requirements for this endpoint technically, QSAR estimations on some representative, known constituents of the UVCB covering at least the whole spectrum of the molecular weight distribution, will be performed.

1. SOFTWARE
EPIWIN software by US-EPA

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

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
Fructose, CAS 57-48-7: O1CC(O)C(O)C(O)C1(O)CO
Smilagenin, CAS 126-18-1: C12(C)C3CCC4(C)C5C(C)C6(OC5CC4C3CCC1CC(O)CC2)OCC(C)CC6
[(3S,8S,9S,10R,13S,14S,16S,17R)-17-Acetyl-3-[(2R,3R,4S,5S,6R)-4-hydroxy-6-(hydroxymethyl)-3,5-bis[[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy]oxan-2-yl]oxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-16-yl] (4R)-2-hydroxy-4-methyl-5-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxypentanoate: CC1C(C(C(C(O1)OC2C(OC(C(C2O)OC3C(C(C(C(O3)C)O)O)O)OC4CCC5(C6CCC7(C(C6CC=C5C4)CC(C7C(=O)C)OC(=O)C(CC(C)COC8C(C(C(C(O8)CO)O)O)O)O)C)C)CO)O)O)O

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- The model and the training and validation sets are published by US Environmental Protection Agency (USA).
The experimental Log Kow values in the training set and validation set were measured using one or more methods equivalent or similar to the following guidelines:
- Shake Flask method (OECD TG 107)
- HPLC method (OECD TG 117)
- Slow Stirring method (OECD TG 123)
Plus relevant EU (1992 as amended) and US EPA OPPTS (1982 as amended) and ASTM (1993) methods may be also used where appropriate.
A full list of experimental Log Kow reference citations is provided in the KOWWIN help menu with additional reference citations.

5. APPLICABILITY DOMAIN
The intended application domain is organic chemicals. Inorganic and organometallic chemicals generally are outside the domain.
The minimum and maximum values for molecular weight are the following:
Training Set Molecular Weights:
Minimum MW: 18.02
Maximum MW: 719.92
Average MW: 199.98

Validation Molecular Weights:
Minimum MW: 27.03
Maximum MW: 991.15
Average MW: 258.98

Currently there is no universally accepted definition of model domain. However, users may wish to consider the possibility that log P estimates are less accurate for compounds outside the MW range of the training set compounds, and/or that have more instances of a given fragment than the maximum for all training set compounds. It is also possible that a compound may have a functional group(s) or other structural features not represented in the training set, and for which no fragment coefficient was developed. These points should be taken into consideration when interpreting model results.

6. ADEQUACY OF THE RESULT
The organic substance Yucca schidigera extract lies mainly within the applicability domain with a molecular weight distribution of 180.16 to 1079 g/mol. The result seems reasonable taking into account the structure of the substances and water solubility. Due to the magnitude of the result, the mostly suitable training set and the considerations leading to this estimation, the result is considered as adequate.

Data source

Reference
Title:
EPI Suite Version 4.10
Year:
2012
Bibliographic source:
KOWWIN - Meylan and Howard (1995)

Materials and methods

Test guideline
Guideline:
other: REACH guidance on QSARs Chapter R.6 , May 2008
Principles of method if other than guideline:
The computer program KOWWIN v1.68 (EPIWIN software by US-EPA) uses the chemical structure of a compound to estimate of the contributions from individual molecular fragments and summing them up to predict the logarithmic octanol-water partition coefficient (logPow).
GLP compliance:
no
Type of method:
calculation method (fragments)
Partition coefficient type:
other:

Test material

Constituent 1
Reference substance name:
Yucca schidigera, ext.
EC Number:
607-033-5
Cas Number:
223749-05-1
IUPAC Name:
Yucca schidigera, ext.

Results and discussion

Partition coefficientopen allclose all
Type:
log Pow
Partition coefficient:
-1.55
Remarks on result:
other: D-Fructose
Type:
log Pow
Partition coefficient:
6.43
Remarks on result:
other: CAS 126-18-1
Type:
log Pow
Partition coefficient:
-4.27
Remarks on result:
other: CC1C(C(C(C(O1)OC2C(OC(C(C2O)OC3C(C(C(C(O3)C)O)O)O)OC4CCC5(C6CCC7(C(C6CC=C5C4)CC(C7C(=O)C)OC(=O)C(CC(C)COC8C(C(C(C(O8)CO)O)O)O)O)C)C)CO)O)O)O
Details on results:
No further details on results are available.

Applicant's summary and conclusion

Conclusions:
This report describes a scientifically accepted calculation method for the partition coefficient using the US-EPA software KOWWIN v1.68 . No GLP criteria are applicable for the usage of this tool and the QSAR estimation is easily repeatable.
Executive summary:

The partition coefficient of the substance Yucca schidigera ext. was determined by the computer program KOWWIN v1.68 (EPIWIN software) by US-EPA (2012). The program uses the chemical structure of a compound to predict the logarithmic octanol water partition coefficient (logPow). The structure is denoted in its SMILES notation. As first step the software determines the logPow contributions from individual molecular fragments. Afterwards these fragments are summed up to gain the logPow for the whole molecule.

In this case a logPow of -1.55 (fructose), 6.43 (Smilagenin) and -4.27 (SMILES CC1C(C(C(C(O1)OC2C(OC(C(C2O)OC3C(C(C(C(O3)C)O)O)O)OC4CCC5(C6CCC7(C(C6CC=C5C4)CC(C7C(=O)C)OC(=O)C(CC(C)COC8C(C(C(C(O8)CO)O)O)O)O)C)C)CO)O)O)O) was determined as result.