Pyridine-2-carbaldehyde

Water solubility

Administrative data

Endpoint:

water solubility

Type of information:

(Q)SAR

Adequacy of study:

key study

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)
WSKOWWIN v1.42

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
O=Cc(nccc1)c1

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
A complete description of the estimation methodology used by WSKOWWIN is available in two documents prepared for the U.S. Environmental Protection Agency, Office of Pollution Prevention and Toxics (Meylan and Howard, 1994a,b).

A journal article that describes the methodology is also available (Meylan et al., 1996). The WSKOWWIN program estimates the water solubility of an organic compound using the compounds log octanol-water partition coefficient (log Kow).

Data Collection
A database of more than 8400 compounds with reliably measured log Kow values had already been compiled from available sources. Most experimental values were taken from a "star-list" compilation of Hansch and Leo (1985) that had already been critically evaluated (see also Hansch et al, 1995) or an extensive compilation by Sangster (1993) that includes many "recommended" values based upon critical evaluation. Other log Kow values were taken from sources located through the Environmental Fate Data Base (EFDB) system (Howard et al, 1982, 1986).  A few values were taken from Section 4a, 8d, and 8e submissions the to U.S. EPA under the Toxic Substances Control Act (see http://www.syrres.com/esc/tscats_info.htm).
 
Water solubilities were collected from the AQUASOL dATAbASETM of the University of Arizona (Yalkowsky and Dannenfelser, 1990), Syracuse Research Corporation's PHYSPROP© Database (SRC,1994), and sources located through the Environmental Fate Data Base (EFDB) system (Howard et al, 1982, 1986). Water solubilities were primarily constrained to the 20-25°C temperature range with 25oC being preferred.

Melting points were collected from sources such as AQUASOL dATAbASETM,  PHYSPROP©, and EDFB as well as the Handbook of Chemistry and Physics (Lide, 1990) and the Aldrich Catalog (Aldrich, 1992).

Regression & Results
A dataset of 1450 compounds (941 solids, 509 liquids) having reliably measured water solubility, log Kow and melting point was used as the training set for developing the new estimation algorithms for water solubility. Standard linear regressions were used to fit  water solubility (as log S) with log Kow, melting point and molecular weight.
Residual errors from the initial regression fit were examined for compounds sharing common structural features with relatively consistent errors. On that basis, 12 compound classes were initially identified and added to the regression to comprise a multi-linear regression including log Kow, melting point and/or molecular weight plus 12 correction factors. Each correction factor is counted a maximum of once per structure [if applicable], no matter how many times the applicable fragment occurs. For example, the nitro factor in 1,4-dinitrobenzene is counted just once. A compound either contains a correction factor or it doesn't; therefore, the matrix for the multi-linear regression contained either a 0 or 1 for each correction factor.
WSKOWWIN estimates water solubility for any compound with one of two possible equations. The equations are equations 19 and 20 from Meylan and Howard (1994a) or equations 11 and 12 from the journal article (Meylan et al., 1996).  The equations are:
    log S (mol/L)  =  0.796 - 0.854 log Kow - 0.00728 MW + ΣCorrections
    log S (mol/L)  =  0.693 - 0.96 log Kow - 0.0092(Tm-25) - 0.00314 MW + ΣCorrections
(where MW is molecular weight, Tm is melting point (MP) in deg C [used only for solids])
When a measured MP is available, that equation is used; otherwise, the equation with just MW is used.

5. APPLICABILITY DOMAIN
The intended application domain is organic chemicals. Inorganic and organometallic chemicals generally are outside the domain.
The WSKOWWIN program applies an individual correction factor only once per structure [if at all] regardless of how many instances of the applicable structural feature occur in the structure. The minimum number of instances is zero and the maximum is one. 

Range of water solubilities in the Training set:
Minimum  =  4 x 10-7 mg/L (octachlorodibenzo-p-dioxin)
Maximum =  completely soluble (various)

Range of Molecular Weights in the Training set:

Minimum  =  27.03 (hydrocyanic acid)
Maximum =  627.62 (hexabromobiphenyl)
 
Range of Log Kow values in the Training set:
Minimum  =  -3.89 (aspartic acid)
Maximum =  8.27 (decachlorobiphenyl)
 

Currently there is no universally accepted definition of model domain. However, users may wish to consider the possibility that water solubility estimates are less accurate for compounds outside the MW range, water solubility range and log Kow range of the 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 correction factor was developed. These points should be taken into consideration when interpreting model results.

6. ADEQUACY OF THE RESULT
The organic substance pyridine-2-carbaldehyde lies within the applicability domain with a molecular weight of 107.11, a logPow of 0.714 and a claculated water solubility of 50240 mg/L. The result seems reasonable taking into account the structure of the substance and its logPow. Due to the magnitude of the result and the suitable training set the result is considered as adequate.

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Reference

Endpoint:

partition coefficient

Type of information:

(Q)SAR

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: scientifically accepted calculation method

Justification for type of information:

QSAR prediction

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

Remarks:

not applicable

Type of method:

calculation method (fragments)

Partition coefficient type:

octanol-water

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.

Executive summary:

The partition coefficient of the substance Pyridine-2 -aldehyde 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 0.5217 was determined as result.

Data source

Reference

Reference Type:

other: software application

Title:

US EPA . Estimation Programs Interface Suite™ for Microsoft® Windows, v 4.10 . United States Environmental Protection Agency, Washington, DC, USA ; WSKOWWIN™ Version 1.42 [2010]

Author:

U.S. Environmental Protection Agency 1200 Pennsylvania Ave., N.W. (Mail Code 7406M) Washington, DC 20460

Year:

2013

Bibliographic source:

http://www.epa.gov/oppt/exposure/pubs/episuite.htm

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 WSKOW v1.42 (EPIWIN software by US-EPA) estimates as first step the octanol-water partition coefficient and based on this value, the water solubility of the chemical is estimated. If relevant, different correction factors are utilized in this procedure.

GLP compliance:

no

Remarks:

not applicable

Type of method:

other: QSAR calculation

Test material

Test material information

Constituent 1

Reference substance name:

Pyridine-2-carbaldehyde

EC Number:

214-333-6

EC Name:

Pyridine-2-carbaldehyde

Cas Number:

1121-60-4

Molecular formula:

C6H5NO

IUPAC Name:

pyridine-2-carbaldehyde

Test material form:

not specified

Details on test material:

Not applicable.

Results and discussion

Water solubility

Water solubility:

50 240 mg/L

Temp.:

25 °C

Remarks on result:

other: based on a logPow value of 0.714 (see cross-reference)

Details on results:

No further details on results are available.

Applicant's summary and conclusion

Conclusions:

Interpretation of results: very soluble (> 10000 mg/L)
The study report describes a scientifically accepted calculation method for the water solubility prediction using the US-EPA software WSkOW v1.42. No GLP criteria are applicable for the usage of this tool and the QSAR estimation is easily repeatable. The substance falls within the applicability domain of the QSAR model, hence, the result can be considered as reliable. The result is adequate for the regulatory purpose.

Executive summary:

The water solubility of the substance Pyridine-2 -aldehyde was determined by the computer program WSKOW v1.42 (EPIWIN software) by US-EPA (2010). As first step, the program calculates the octanol-water partition coefficient and predicts subsequently the water solubility of the chemical compound. If relevant, the software utilizes different correction factors in these predictions.

For the chemical a water solubility of 50240 mg/L (5.024 e+004 mg/L) was calculated based on a experimental logPow of 0.714 (see cross-reference). No correction factors were presented. Due to this estimation the substance is regarded to be very soluble in water.

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.