Ichthammol

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

key study

Study period:

April to May 2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

In the literature Sulfonated Shale Oils (such as Ichthammol) are described as viscous, brown-blackish, neutral liquids of characteristic odor. Their status as liquids results from the fact that water appearing as a by-product in course of the manufacturing process (sulfonation and neutralization of a distillate resulting from destructive distillation of organic matter rich limestones) is considered an intrinsic part of the substance.

With all water removed what remains is the so-called “dry matter”, a solid which is composed of sulfonated (alkylated) aromatic salts with thiophene derivatives as the main heterocyclic entities.

The main compounds have surfactant properties with the oil based organic part being lipophilic and the sulfonate group being of hydrophilic nature (R-SO2-ONH4). As a surfactant Ichthammol is capable of forming emulsions with oils. In fact, Ichthammol itself can be regarded as an emulsion as unsulfonated oil is part of the substance to some extent.

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 formation of a third phase between octanol and water is observed (emulsion). However, based on colouring of the (clouded) water and octanol phase a partition coefficient can be calculated.

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).

In this case Ichthammol was added to a mixture of equal volumes of octanol and water. From colouring of the two phases the concentration of Ichthammol is deduced and the partition coefficient calculated.

GLP compliance:

yes

Remarks:

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

Other quality assurance:

other: GMP

Type of method:

estimation method (solubility ratio)

Partition coefficient type:

octanol-water

Test material

Test material information

1

Reference substance name:

Ichthammol

EC Number:

232-439-0

EC Name:

Ichthammol

Cas Number:

8029-68-3

Molecular formula:

unspecified

IUPAC Name:

Ichthammol (UVCB substance)

Test material form:

liquid: viscous

Details on test material:

sample from a batch from regular production released for use as an active pharmaceutical ingredient in medicinal products.

Specific details on test material used for the study:

batch 2/18 from regular production at registrant's manufacturing site

Study design

Analytical method:

other: concentration correlation based on colouring of octanol and water phase and solubility testing with classification according to European Pharmacopoeia, 9th edition, 2018, chapter 1.4

Results and discussion

Partition coefficient

Key result

Type:

log Pow

Partition coefficient:

ca. -0.4

Temp.:

20 °C

pH:

>= 6 - <= 7.5

Applicant's summary and conclusion

Conclusions:

Assessment of the partition coefficient by correlating the color of water and octanol phase results in a log Pow of less than zero (-0.4). This result is in line with what is known about partition coefficients of surfactants with a known molecular structure (as e.g. sodium laureth sulfates). Ichthammol has properties of a surfactant as it is composed of sulfonated shale oil fractions mainly in its "dry matter".