Ichthyolic acid, sodium salt

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

key study

Study period:

February to March 2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

Ichthyolic Acid, Sodium Salt (former INCI: sodium shale oil sulfonate) is a surfactant of amphiphilic nature. As a UVCB substance it contains a large variety of organic (thiophene based) sulfonate entities based on a defined shale oil fraction. Due to the extreme complexity of the substance resolution of the molecular structures is not possible. It can be assumed that the substance is largely ionized in water. In a octanol-water mixture emulsion formation is observed with clouding of both phases.

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: COUNCIL REGULATION (EC) No 440/2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 (REACH): A.8. PARTITION COEFFICIENT Appendix I Estimation Method

Version / remarks:

30 May 2008

Deviations:

not applicable

Principles of method if other than guideline:

Solubility of substances is addressed in chapter 1.4 of the European Pharmacopoeia (9th edition, 2018). The approximate volume of solvent in millilitres per gram of solute is taken as a measure for the extent of solubility. Solubility is checked in such a way that ratios of solvent and solute are prepared in order to facilitate classification of a test substance with regard to the descriptive term (e.g. “practically insoluble” if more than 10000 ml of solvent per gram of solute is needed). As ICHTHYOL PALE (as a trademark substance of Ichthyolic Acid, Sodium Salt) is distinguished by a brownish-black color as pure raw material, it can be visually controlled if a homogenous solution can be achieved or not (e.g. colored sediment in flask).

GLP compliance:

yes

Remarks:

Quality Control Laboratory in a GMP certified pharmaceutical manufacturer (quality standard comparable to GLP)

Other quality assurance:

other: GMP

Remarks:

The laboratory is active in quality control of ICHTHYOL substances (entrance inspection, release, stability studies) in a GMP environment

Type of method:

estimation method (solubility ratio)

Partition coefficient type:

octanol-water

Test material

Test material information

Constituent 1

Reference substance name:

Ichthyolic acid, sodium salt

EC Number:

215-671-7

EC Name:

Ichthyolic acid, sodium salt

Cas Number:

1340-06-3

IUPAC Name:

Identification of the UVCB substance by "Chemcial Abstracts Index Name", among others: Ichthyolic Acid, Sodium Salt. No IUPAC name known.

Test material form:

liquid

Specific details on test material used for the study:

ICHTHYOL PALE batch 0041117208Ö3/17

batch from regular production at ÖSTERREICHISCHE ICHTHYOL (registrant's manufactcuring site)

Sample used was taken from bulk material as delivered to ICHTHYOL-GESELLSCHAFT Cordes, Hermanni & Co. (GmbH & Co.) KG for repacking and worldwide distribution.

Based on stability studies („Note for Guidance on Stability Testing of Existing Active Substances and Related Finished Products” (EMEA “CPMP/QWP/122/02, Corr. dated November 2002) no special storage conditions apply. Especially, ICHTHYOL® PALE is not susceptible to water vapour in the ambient air as it is a raw material consisting of up to 50% of water. Under storage conditions at the different storage temperatures a thermodynamic equilibrium develops between liquid and gas phase with saturation vapour pressure of water vapour in the gas phase. The corresponding humidity should be considerably higher than the ones proposed in the above mentioned “Note for Guidance” (e.g. 60% or 65% RH). For this reason, penetration of water from outside is not likely. However, as outwards penetration (inside -> outside) may occur instead, the dry matter of ICHTHYOL® PALE is one of the parameters regularly examined during storage.
For the batch used in solubility testing compliance with specification parameters (including dry matter) is confirmed by a certificate of analysis signed by quality control units of both ÖSTERREICHISCHE ICHTHYOL in Reith bei Seefeld, Austria, and ICHTHYOL-GESELLSCHAFT in Hamburg, Germany.

Study design

Analytical method:

other: solubility testing with classification according to the European Pharmacopoeia, 9th edition, 2018, chapter 1.4

Results and discussion

Partition coefficient

Key result

Type:

log Pow

Partition coefficient:

< 0

Temp.:

20 °C

pH:

>= 6 - <= 7.5

Applicant's summary and conclusion

Conclusions:

It is not possible to obtain a clear solution of Ichthyolic Acid, Sodium Salt in n-octanol. Even in a concentration of less than 0.1% a colored sediment is observed in the flask. This is in line with the descriptive term "practically insoluble" according to the European Pharmacopoeia. As ICHTHYOL PALE is obtained by sulfonation of a sulfur-rich shale oil fraction with a wide boiling range comprising about 100°C at a pressure of 0.1 hPa, there may be compounds at least partly soluble in n-octanol. However, no coloring of the solvent phase can be detected. Solubility therefore should be less than 0.1 g/l.
On the other hand, ICHTHYOL PALE is soluble in water in all ratios applied (solute:solvent = 3:7, 5:5, 9:1). We, therefore, can assume that ICHTHYOL PALE at least is "freely soluble" in water which is in line with a concentration of more than 900 g/l.
If these solubility limits are taken for an estimation of the partition coefficient we obtain log Pow of less than zero (< 0).
The same result can be obtained when considering the topic from another perspective. ICHTHYOL PALE is a mixture of a sulfonate salt with water (which results as a by-product in the manufacturing process). In fact, about 50% of water can be found besides so-called "dry matter", i.e. ICHTHYOL PALE can be regarded as a 50% solution (corresponding to a solution of about 500 g/l). By evaporation there may appear a ratio of dry matter to water which results in precipitation of compounds belonging to the "dry matter". However, for the purpose of estimation of a partipition coefficient such an information is irrelevant because again a very poor solubility of ICHTHYOL PALE in n-octanol has to be related to very high solubility of ICHTHYOL PALE in water. And again the log Pow is estimated to be below zero.
As the composition of "dry matter" in ICHTHYOL PALE is not available due to the high complexity of it, there is no way for calculation of a partition coefficient. Determination of the partition coefficient by a practical analytical method is not feasible due to the surface activity of ICHTHYOL PALE. However, the estimated partition coefficient of < 0 is in line with what is known about partition coefficients of surfactant with a better known molecular structure (as e.g. sodium laureth sulfates).