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Partition coefficient

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Endpoint:
partition coefficient
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
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
CC(OCC1CO1)C

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 Isopropylglycidether lies within the applicability domain with a molecular weight of 116.16. All available fragments of Isopropylglycidether are either contained in the KOWWIN training set, or suitable "correction factors” are available to refine the lower predictivity for substances containing these fragments. The result seems reasonable taking into account the structure of the substance, its water solubility of 19 g/L and the experimental database value of LogKow = 0.8. Due to the magnitude of the result and the suitable training set the result is considered as adequate.
Guideline:
other: REACH guidance on QSARs Chapter R.6 , May 2008
Principles of method if other than guideline:
Meylan, W.M. and P.H. Howard. 1995. Atom/fragment contribution method for estimating octanol-water partition coefficients. J. Pharm. Sci. 84: 83-92
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
Remarks:
(not applicable)
Type of method:
calculation method (fragments)
Partition coefficient type:
octanol-water
Key result
Type:
log Pow
Partition coefficient:
0.52
Remarks on result:
other: no temperature and pH are given
Details on results:
No further details on results are available.
Conclusions:
The study 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. The result is adequate for the regulatory purpose, and the magnitude of the result is considered scientifically reasonable taking into account the available information on logPow, water solubility, structure and molecular weight.
Executive summary:

The partition coefficient of the substance 2-(isopropoxymethyl)oxirane 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 0.52 was determined as result.

Adequacy of the QSAR:

- QSAR model is scientifically valid.

- The substance falls within the applicability domain of the QSAR model.

- The prediction is fit for regulatory purpose.

Endpoint:
partition coefficient
Type of information:
other: publication
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Peer-reviewed database
Principles of method if other than guideline:
shake-flask method
GLP compliance:
not specified
Type of method:
flask method
Partition coefficient type:
octanol-water
Analytical method:
other: gas-liquid chromatography
Key result
Type:
log Pow
Partition coefficient:
0.8
Temp.:
25 °C
Remarks on result:
other: (no pH given)
Details on results:
No further details are available.
Conclusions:
A logPow of 0.80 is reported (no pH given).
Executive summary:

The octanol-water partition coefficient is reported in the databank of evaluated octanol-water partition coefficients (LOGKOW) and was determined by Boikov, Shibaev, Gaidamaka and Výunov in 1989 by the shake-flask method. The logPow is reported as 0.80 for the test substance (no pH given).

Endpoint:
partition coefficient
Type of information:
other: publication
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Authoritative secondary source; applicability domain not assessable
Principles of method if other than guideline:
Calculation with ACD Labs software v11.02, which provides structure-based predictions physicochemical properties, ADME and toxicity parameters, NMR spectra & nomenclature.
GLP compliance:
no
Remarks:
(not applicable)
Type of method:
other: QSAR estimation
Partition coefficient type:
octanol-water
Key result
Type:
log Pow
Partition coefficient:
0.712
Temp.:
25 °C
Remarks on result:
other: ±0.394 , Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (© 1994-2012 ACD/Labs)
Details on results:
No further details available
Conclusions:
Log Pow : 0.712±0.394 (25°C)
Executive summary:

The partition coefficient of the substance Oxirane, 2-[(1-methylethoxy)methyl]- was calculated by the computer program Advanced Chemistry Development (ACD/Labs) Software V11.02 (© 1994-2012 ACD/Labs) .

A logPow of 0.712±0.394 at 25°C was obtained as result.

Description of key information

LogPow: Sangster logPOW database, experimental value, shake flask: logPow = 0.8 @ 25°C

LogPow: EpiSuite estimation, KOWWIN v1.68: logPow = 0.52

LogPow: Database entry, ACD Labs software v11.02 estimation: logPow = 0.712 ± 0.394 @ 25°C

Key value for chemical safety assessment

Log Kow (Log Pow):
0.8
at the temperature of:
25 °C

Additional information

The chosen key value of logPow = 0.8 at 25°C for risk assessment is the only available experimental value. Both available QSAR estimation revealed values of 0.52 and 0.71 using suitable models for the present structure, which are very close to the experimental one. This consistency indicates, too, that the available results can be considered as sufficiently reliable for further risk assessment. Also, the experimental value of 0.8 being the highest one represents the safer approach for risk assessment, avoiding an underestimation of the accumulation potential of the substance.