DL-alanine

Adsorption / desorption

Link to relevant study record(s)

Reference

Endpoint:

adsorption / desorption, other

Remarks:

adsorption/desorption

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2019-08-13

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: accepted calculation method

Justification for type of information:

QSAR prediction

Qualifier:

according to guideline

Guideline:

other: (Q)SAR calculation of log Koc with software program KOCWIN v 2.00, part of the software package EPIWIN 4.11 Suite, Version 4.11, U.S. Environmental Protection Agency copyright © 2012

Version / remarks:

KOCWIN v2.00

Deviations:

no

Principles of method if other than guideline:

- Software tool(s) used including version: EPIsuite v4.11
- Model(s) used: KOCWIN as part of EPIsuite
- Model description: see field 'Justification for non-standard information', 'Attached justification' and/or 'Cross-reference' : The substance evaluated falls within the
Koc is calculated using a measured
- Justification of QSAR prediction: see field 'Justification for type of information', 'Attached justification' and/or 'Cross-reference'

GLP compliance:

no

Type of method:

other: (Q)SAR calculation

Media:

other: no data

Computational methods:

PCKOCWIN (version 2) estimates Koc with two separate estimation methodologies:
(1) estimation using first-order Molecular Connectivity Index (MCI)
(2) estimation using log Kow (octanol-water partition coefficient)

The Koc QSAR is based on a database of measured values.

6.1.1. Collection of Koc Data
The major source of experimental Koc data was Schuurmann et al. (2006) which includes a compilation of selected Koc values for 571 compounds.  Data from the original PCKOWIN regression (that included a total of 389 compounds) were also used.  A new data source was the USDA Pesticide Properties Database (data for more than 150 compounds were collected).  Koc values for a few additional compounds were collected from references in Environmental Fate Data Base system (Howard et al., 1982, 1986).

For compounds appearing in more than one of the various compilations, a single Koc value was selected.  In general, values from the Schuurmann et al. (2006) compilation were used.  An average value was used for a few compounds.

After some additional quality control to ensure various reported Koc values were not estimated (as opposed to experimental), selected Koc values for 674 compounds were used to train and validate the updated regression from these sources:
(1) Schuurmann et al. (2006) compilation:  453 compounds
(2)  Original PCKOCWIN regression:  85 compounds
(3) USDA Pesticide Properties Database :  85 compounds
(4)  Average from multiple sources:  21 compounds
(5)  Miscellaneous sources:  30 compounds  (Nguyen et al, 2005; Sabljic et al, 1995; Baker et al, 1997; VonOepen et al, 1991; Kaune, 1998; Gawlik et al, 1998; HSBD, 2008)

The 674 compounds were eventually divided into a training set of 516 compounds and a validation set of 158 compounds.  The training set was divided further into a dataset of 69 non-polar organics and 447 polar organics (same as previously described in Meylan et al, 1992).  For the current model development, the non-polar dataset is designated as compounds having "No Correction Factors" while the polar compounds are designated as compounds "Having Correction factors".

6.1.2. Estimation Using Molecular Connectivity Index

PCKOCWIN (version 1) estimated Koc solely with a QSAR utilizing Molecular Connectivity Index (MCI).  This QSAR estimation methodology is described completely in a journal article (Meylan et al, 1992) and in a report prepared for the US EPA (SRC, 1991).  PCKOCWIN (version 2) utilizes the same methodology, but the QSAR has been re-regressed using a larger database of experimental Koc values that includes many new chemicals and structure types.

6.1.3. Estimation Using Log Kow
A traditional method of estimating soil adsorption Koc involves correlations developed with log octanol-water partition coefficient (log Kow) (Doucette, 2000).  Since an expanded experimental Koc database was available from the new MCI regression, it was decided to develop a log Kow estimation methodology that was potentially more accurate than existing log Kow QSARs for diverse structure datasets.

Effectively, the new log Kow methodology simply replaces the MCI descriptor with log Kow and derives similar equations.  The derivation uses the same training and validation data sets.  The training set is divided into the same non-polar (no correction factors) and correction factor sets.  The same correction factors are also used.

Separate equations correlating log Koc with log Kow were derived for nonpolar and polar compounds because it was statistically more accurate to do so than to use the approach taken with the MCI-based method.  The equation derived by the non-polar (no correction factor) regression is:
log Koc  =  0.8679 Log Kow  -  0.0004
(n = 68, r2 = 0.877, std dev = 0.478, avg dev = 0.371)

One non-polar compound was removed from the regression (hexabromobiphenyl) because it was the only compound without a recommended experimental log Kow and the accuracy of its estimated log Kow (9.10) is suspect.  This equation is used for any compound having no correction factors.

For the multiple-linear regression using correction factors, log Kow was included as an individual descriptor.  For compounds having correction factors, the equation is:
 log Koc  =  0.55313 Log Kow  +  0.9251 + ΣPfN  
where ΣPfN is the summation of the products of all applicable correction factor coefficients from Appendix D multiplied by the number of times (N) that factor is counted for the structure.

The accuracy of the log Kow estimation methodology is described in the Accuracy & Domain Section (Section 6.2).

See Appendix E, Appendix F and Appendix G for  lists of the chemicals used in the regressions and a supplemental validation list.
 
6.2.  Accuracy & Domain
6.2.1.  Statistical Accuracy

The following table gives statistical information for the log Kow-based regression: training and validation sets.  The statistics pertain to the experimental log Koc and the Log Kow estimated log Koc:

Log Kow Methodology
Training Training Validation
No Corrections with Corrections Data set
number 68 447 150 **
r2 corr coef 0.877 0.855 0.778
std deviation 0.478 0.396 0.679
avg deviation0.371 0.307 0.494

** eight ammonium and metal salt compounds were removed from the Validation dataset

Overall, the MCI methodology is somewhat more accurate than the Log Kow methodology, although both methods yield good results.  If the Training datasets are combined in to one dataset of 516 compounds (69 having no corrections plus 447 with corrections), the MCI methodology has an r2, standard deviation and average deviation of 0.916, 0.330 and 0.263, respectively, versus 0.86, 0.429 and 0.321 for the Log Kow methodology.

Type:

log Koc

Value:

-1.44

Temp.:

20 °C

Remarks on result:

other: calculation

Type:

Koc

Value:

0.036

Temp.:

20 °C

Remarks on result:

other: calculation

KOCWIN Program (v2.00) Results:

==============================

SMILES : O=C(O)C(N)C

CHEM   : DL-Alanine

MOL FOR: C3 H7 N1 O2

                Koc may be sensitive to pH!

---------------------------  KOCWIN v2.00 Results  ---------------------------

 Koc Estimate from MCI:

 ---------------------

        First Order Molecular Connectivity Index  ........... :  2.643

        Non-Corrected Log Koc (0.5213 MCI + 0.60)  .......... :  1.9775

        Fragment Correction(s):

                 1   Nitrogen to Carbon (aliphatic) (-N-C)..  : -0.2127

                 *   Organic Acid  (-CO-OH)  ...............  : -1.6249

        Corrected Log Koc  .................................. :  0.1399

                        Estimated Koc:  1.38  L/kg   <===========

 Koc Estimate from Log Kow:

 -------------------------

        Log Kow  (User entered   )  ......................... : -2.85

        Non-Corrected Log Koc (0.55313 logKow + 0.9251)  .... : -0.6513

        Fragment Correction(s):

                 1   Nitrogen to Carbon (aliphatic) (-N-C)..  : -0.0218

                 *   Organic Acid  (-CO-OH)  ...............  : -0.7694

        Corrected Log Koc  .................................. : -1.4425

                        Estimated Koc:  0.0361  L/kg   <===========

  ********************************************************************

  *                            NOTE:                                 *

  * The Koc of this structure may be sensitive to pH!  The estimated *

  * Koc represents a best-fit to the majority of experimental values *

  * however, the Koc may vary significantly with pH.                 *

  ********************************************************************

Conclusions:

The calculated adsorption/desorption coefficient Koc of DL and L-alanine is ca. 0.036 (log Koc: ca. -1.44). This calculation is based on the measured Log Kow of -2.85.
The estimated result shows that the substance has no environmental impact.

Executive summary:

The calculated adsorption/desorption coefficient Koc of DL and L-alanine is ca. 0.036 (log Koc: ca. -1.44). This calculation is based on the measured Log Kow of -2.85 (Sangster, 1994).

Description of key information

The calculated adsorption/desorption coefficient Koc of DL and L-alanine is ca. 0.0361 L/kg

The estimated result shows that the substance has no environmental impact.

In accordance with REACH Annex VIII section 9.3.1. column 2 and Annex IX section 9.3.3. column 2, further studies do not need to be conducted as the substance has a low log Kow as well as the substance and its degradation products decompose rapidly.

Key value for chemical safety assessment

Koc at 20 °C:

0.036

Additional information

The calculated adsorption/desorption coefficient Koc of L-alanine is ca. 0.0361 (log Koc: ca. -1.4425) using the measured log Kow of -2.85 (Sangster 1994) as starting point. This estimated result shows that the substance is mobile.

The log Koc was calculated by EpiSuite's KOCWIN model. The suitability of the model was assessed and it was concluded that L-alanine is considered to be inside the applicability domain of the EpiSuite KOCWIN model.

In accordance with REACH Annex VIII section 9.3.1. column 2 and Annex IX section 9.3.3. column 2, further studies do not need to be conducted as the substance has a low log Kow as well as the substance and its degradation products decompose rapidly.