Registration Dossier

Administrative data

Endpoint:
partition coefficient
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
2018-03-23
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:
The substance is manufactures and distributed as an approx. 50% aqueous solution in water. The solid is hence highly soluble in water, i.e. min. 500 g/l. Taking into account the magnitude of this result, the registered substance is expected to have a negative logPow, which makes an experimental determination (given the magnitude) not necessary or possibly not even feasible, and a well-documented QSAR estimation of the logPow of the contained solid is considered sufficient.

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
The substance is a organic UVCB manufactured by reaction of butin-2-diol-1,4, sodium hydroxide and propanesultone using water as solvent. The CAS number 90268-78-3 (EC 290-883-0) is associated with the inventory name 2-Butyne-1,4-diol, reaction products with 1,2-oxathiolane 2,2-dioxide and sodium hydroxide (HBOPS-Na), the molecular formula cannot be given. As indicated by the name, there are several reaction products possible, resulting in a variable composition. Below there are the possible individual components with approximate contents listed:

CAS No Content, approx. Name Molecular formula Molecular weight SMILES notation
75032-91-6 48% sodium 3-[(4-hydroxybut-2-yn-1-yl)oxy]propane-1-sulfonate C7H12O5S.Na 230.214 [Na+].OCC#CCOCCCS(=O)(=O)[O-]
3542-44-7 7.6% sodium 3-hydroxypropane-1-sulphonate C3H7O4S.Na 162.14 [Na+].OCCCS(=O)(=O)[O-]
110-65-6 12.6% but-2-yne-1,4-diol C4H6O2 86.0892 OCC#CCO
n/a 31.8% disodium 3-[4-[3-sulfonatopropoxy)but-2-ynox]propane-1-sulfonate (“Dimer”) C10H16Na2O8S2 374.3438 O=S(=O)([O-])CCCOCC#CCOCCCS(=O)(=O)[O-].[Na+].[Na+]

QSAR estimations are performed for all contained structures

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 UVCB substance 2-Butyne-1,4-diol, reaction products with 1,2-oxathiolane 2,2-dioxide and sodium hydroxide (HBOPS-Na) lies within the applicability domain with a molecular weight of 86.09 – 374.34 g/mol, considering the molecular weights of its single constituents. The results seem reasonable taking into account the structure of the substance(s) and water solubility. Due to the magnitude of the result and the suitable training set the result is considered as adequate.

Data source

Reference
Title:
EPI Suite Version 4.10
Year:
2018
Bibliographic source:
KOWWIN - Meylan and Howard (1995)

Materials and methods

Test guideline
Guideline:
other: REACH guidance on QSARs Chapter R.6
Version / remarks:
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
GLP compliance:
no
Remarks:
not required
Type of method:
calculation method (fragments)
Partition coefficient type:
octanol-water

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Results and discussion

Partition coefficientopen allclose all
Key result
Type:
log Pow
Partition coefficient:
-5.02
Remarks on result:
other: for Sodium 3-[(4-hydroxybut-2-yn-1-yl)oxy]propane-1-sulfonate
Remarks:
QSAR predicted value
Key result
Type:
log Pow
Partition coefficient:
-5.01
Remarks on result:
other: for Sodium 3-hydroxypropane-1-sulphonate
Remarks:
QSAR predicted value
Key result
Type:
log Pow
Partition coefficient:
-0.93
Remarks on result:
other: for But-2-yne-1,4-diol
Remarks:
QSAR predicted value
Key result
Type:
log Pow
Partition coefficient:
-5.49
Remarks on result:
other: for Disodium 3-[4-[3-sulfonatopropoxy)but-2-ynox]propane-1-sulfonate
Remarks:
QSAR predicted value

Applicant's summary and conclusion

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.
Executive summary:

The partition coefficient of the substance 2-Butyne-1,4-diol, reaction products with 1,2-oxathiolane 2,2-dioxide and sodium hydroxide (HBOPS-Na) resp. its single constituents 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 the following logPow values were determined as result:

Sodium 3-[(4-hydroxybut-2-yn-1-yl)oxy]propane-1-sulfonate:-5.02

Sodium 3-hydroxypropane-1-sulphonate:-5.01

But-2-yne-1,4-diol:-0.93

Disodium 3-[4-[3-sulfonatopropoxy)but-2-ynox]propane-1-sulfonate:-5.49

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.