Lithium chloride

Partition coefficient

Link to relevant study record(s)

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: see 'Remark'

Remarks:

According to REACH Regulation (EC) No 1907/2006, Annex XI, section 1.3, the used QSAR model needs to be scientifically validated and the substance has to fit in the applicability domain of the used model. EPI Suite v4.10 is a collection of physical/chemical property and environmental fate estimation models developed by the EPA’s Office of Pollution Prevention Toxics and Syracuse Research Corporation (SRC). It is a screening level tool which gives adequate results for the purpose of classification and labelling and/or risk assessment. In addition, the used QSAR estimation tool is recommended by ECHA and can be found in Table R.7.1-21 in the REACH Guidance on information requirements and chemical safety assessment (2008), chapter R.7.1.7.3., thus the calculated value is reliable with restrictions.

Guideline:

other: QSAR Estimation with KOWWIN v1.68

Deviations:

no

Principles of method if other than guideline:

KOWWIN uses a "fragment constant" methodology to predict log P. In a "fragment constant" method, a structure is divided into fragments (atom or larger functional groups) and coefficient values of each fragment or group are summed together to yield the log P estimate. KOWWIN’s methodology is known as an Atom/Fragment Contribution (AFC) method. Coefficients for individual fragments and groups were derived by multiple regression of 2447 reliably measured log P values. To estimate log P, KOWWIN initially separates a molecule into distinct atom/fragments. In general, each non-hydrogen atom (e.g. carbon, nitrogen, oxygen, sulfur, etc.) in a structure is a "core" for a fragment; the exact fragment is determined by what is connected to the atom. Several functional groups are treated as core "atoms"; these include carbonyl (C=O), thiocarbonyl (C=S), nitro (-NO2), nitrate (ONO2), cyano (-C/N), and isothiocyanate (-N=C=S). It became apparent, for various types of structures, that log P estimates made from atom/fragment values alone could or needed to be improved by inclusion of substructures larger or more complex than "atoms"; hence, correction factors were added to the AFC method. The term "correction factor" is appropriate because their values are derived from the differences between the log P estimates from atoms alone and the measured log P values.
Two separate regression analyses were performed. The first regression related log P to atom/fragments of compounds that do not require correction factors (i.e., compounds estimated adequately by fragments alone). The general regression equation has the following form:

log P = Σ(f*n) + b (Equation 1)

where Σ(f*n) is the summation of f (the coefficient for each atom/fragment) times n (the number of times the atom/fragment occurs in the structure) and b is the linear equation constant. This initial regression used 1120 compounds of the 2447 compounds in the total training dataset. The correction factors were then derived from a multiple linear regression that correlated differences between the experimental (expl) log P and the log P estimated by Equation 1 above with the correction factor descriptors. This regression did not utilize an additional equation constant. The equation for the second regression is:

log P (expl) - log P (eq 1) = Σ(c*n) (Equation 2)

where Σ(c*n) is the summation of c (the coefficient for each correction factor) times n (the number of times the correction factor occurs (or is applied) in the molecule).
Results of the two successive multiple regressions (first for atom/fragments and second for correction factors) yield the following general equation for estimating log P of any (organic) compound:

log P = Σ(f*n) + Σ(c*n) + 0.229 (Equation 3)

(num = 2447, r2 = 0.982, std dev = 0.217, mean error = 0.159)

GLP compliance:

not specified

Type of method:

other: Atom/Fragment Contribution method

Partition coefficient type:

octanol-water

Key result

Type:

log Pow

Partition coefficient:

ca. -0.46

Temp.:

20 °C

Remarks on result:

other: Data set taken for estimation was derived at temperatures between 20 - 25°C. No pH value was indicated.

Details on results:

The minimum and maximum values for molecular weight that are covered by the model are for the training set compounds (2447 compounds) 18.02 to 719.92 g/mol. For the validation set compounds (10946 compounds) it is 27.03 to 991.15 g/mol.

Conclusions:

A log Pow of -0.46 was estimated for lithium chloride using the EPI Suite v4.10.

Executive summary:

Lithium chloride quickly dissociates in water forming lithium and chloride ions. Therefore a laboratory study determining the partition coefficient is technically not feasible. The calculation of the partition coefficient of lithium chloride with EPI Suite v4.10 can be seen as rough estimation as only a few inorganic compounds were included in the training data set of the program. But taken into account the quick dissociation of lithium chloride in water this EPI Suite estimation can be regarded as adequate enough to be used for the risk assessment.

The partition coefficient of lithium chloride was estimated using KOWWIN v1.68 embedded in EPI Suite v4.10 of EPA’s Office of Pollution Prevention Toxics and Syracuse Research Corporation (SRC). The program is a screening level tool and estimates the log octanol/water partition coefficient log Pow of chemicals using an atom/fragment contribution method. Lithium chloride has a molecular weight of 42.395 g/mol and therefore fits the applicability domain of this model. A log Pow of -0.46 was derived for the test item.

Description of key information

According to column 2 of REACH Regulation (EC) No 1907/2006, Annex VII, section 7.8, the test on partition coefficient n-octanol/water does not need to be conducted as lithium chloride is an inorganic compound. Further, the theoretical, calculated log Pow is given in the supporting study report.

Key value for chemical safety assessment

Log Kow (Log Pow):

-1

Additional information

Lithium chloride quickly dissociates in water forming lithium and chloride ions. Therefore a laboratory study determining the partition coefficient is technically not feasible. The calculation of the partition coefficient of lithium chloride with EPI Suite v4.10 can be seen as rough estimation as only a few inorganic compounds were included in the training data set of the program. But taken into account the quick dissociation of lithium chloride in water this EPI Suite estimation can be regarded as adequate enough to be used for the risk assessment.

The partition coefficient of lithium chloride was estimated using KOWWIN v1.68 embedded in EPI Suite v4.10 of EPA’s Office of Pollution Prevention Toxics and Syracuse Research Corporation (SRC). The program is a screening level tool and estimates the log octanol/water partition coefficient log Pow of chemicals using an atom/fragment contribution method. Lithium chloride has a molecular weight of 42.395 g/mol and therefore fits the applicability domain of this model. A log Pow of -0.46 was derived for the test item.

For CSR preparation, the log Pow of - 1 (EUSES default value) was used.