5,5'-{ethane-1,2-diylbis[thio-1,3,4-thiadiazole-5,2-diyldiazene-2,1-diyl(5-amino-3-tert-butyl-1H-pyrazole-4,1-diyl)]}diisophthalic acid

Solubility in organic solvents / fat solubility

Administrative data

Endpoint:

solubility in organic solvents / fat solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Study initiated 16th February. Experimental phase 23rd February until 21st April. Study report finalised 12th July 2011.

Reliability:

1 (reliable without restriction)

Justification for type of information:

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The read-across is based on the hypothesis that the Source and Target substances will have similar toxicological and ecotoxicological properties, due to their extremely close physico-chemical properties and structural similarities. For example, both the Source and Target substances are mono-constituents which share structural similarities and contain the same functional groups.
The Source substance has a comprehensive data set generated for a REACH Annex VII registration and this along with its similarity to the Target substance are considered sufficient to consider the read-across an appropriate adaptation to the standard information requirements of Annex VII of the REACH regulation for the Target substance in accordance with the provisions of Annex XI, 1.5 of the REACH regulation.
As can be seen from the structure the Source substance and the Target substance are structurally identical the difference lies in the salt form i.e. the counter ion. In the case of the Source substance the counter ion is a potassium ion whereas in the Target substance the counter ion is a hydrogen .
SOURCE TARGET
mono-constituent substance mono-constituent substance

Potassium salt
Free acid


Both the Source and Target substances have similar molecular weights of 1073 and 921 respectively. The difference in molecular weight is due to the counter ions. The Source substance is the potassium salt of the Target substance.


2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)

The Source and Target substance have similar purity profiles. Water is the main impurity in both substances. Both substances contain impurities that are analogues of the Source molecule. Neither substance contains purposely added diluents or additives.
The Source and Target are manufactured using the same chemical synthetic route. The difference in salt form is the difference between the two substances.

3. ANALOGUE APPROACH JUSTIFICATION
The Target substance is the free acid salt of the Source substance, hence the Target contains all the same functional groups as the Source substance. It is anticipated that the physicochemical results of the Target and the Source substance will be very similar.
It is expected that the water solubility of the Target Substance will be slightly lower than the Source substance, although environmental conditions will impact on the degree of solubility. Even though the water solubility values are differ , both the Source and Target substance are extremely water soluble and neither will have a tendency to partition into lipids or body fats. The potential for systemic absorption is considered to be low for both substances as their bioavailability is expected to be low due to the high molecular weights of the molecules and low lipophilicity, which precludes easy passage across biological membranes.
For the full read across assessment dossier see the attached Read-across assessment framework report


4. DATA MATRIX
See Read-Across Assessment Framework Report

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

no guideline available

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Tetra potassium 5,5'-[ethane-1,2-diylbis[thio-1,3,4-thiadiazole-5,2-diyldiazene-2,1-diyl(5-amino-3-tert-buyl-1H-pyrazole-4,1-diyl)]}diisophthalate

EC Number:

700-616-6

Cas Number:

849608-59-9

Molecular formula:

C36H32K4N14O8S4

IUPAC Name:

Tetra potassium 5,5'-[ethane-1,2-diylbis[thio-1,3,4-thiadiazole-5,2-diyldiazene-2,1-diyl(5-amino-3-tert-buyl-1H-pyrazole-4,1-diyl)]}diisophthalate

Test material form:

solid

Results and discussion

Solubility in organic solvents / fat solubility

Solubility in organic solvents / fat solubility 1

Key result

Medium:

other: chloroform

Solubility:

< 0.2 other: µg/ml

Temp.:

25 °C

Solubility in organic solvents / fat solubility 2

Key result

Medium:

other: n-hexane

Solubility:

< 0.2 other: µg/ml

Temp.:

25 °C

Solubility in organic solvents / fat solubility 3

Key result

Medium:

acetone

Solubility:

< 1 other: µg/ml

Temp.:

25 °C

Solubility in organic solvents / fat solubility 4

Key result

Medium:

ethanol

Solubility:

< 2 800 other: µg/ml

Temp.:

25 °C

Test substance stable:

yes

Applicant's summary and conclusion

Conclusions:

The test substance was most soluble in ethanol.

Executive summary:

Introduction

The solubility of the test substance in various volatile solvents.

Method

The sample was ground before use. An initial assessment was made by adding 0.1g of test substance into 14ml Trident vials and adding 10ml of each solvent. The flasks were stirred overnight at 25ºC and the samples were then filtered and the solvent evaporated. The samples were examined on a Perkin Elmer Lambda 900 UV/Visible spectrometer and compared with a graph prepared in distilled / deionised water at 427nm.

Results and conclusions

The test substance was most soluble in ethanol.