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

Partition coefficient

Administrative data

Endpoint:

partition coefficient

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)

Rationale for reliability incl. deficiencies:

guideline study

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:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient)

Deviations:

no

GLP compliance:

yes

Type of method:

shake-flask method to: flask method

Partition coefficient type:

octanol-water

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

Study design

Analytical method:

other: perkin elmer lambda 900 UV/VIS/NIR

Results and discussion

Partition coefficient

Key result

Type:

log Pow

Partition coefficient:

< -2.7

Temp.:

25 °C

pH:

ca. 7

Any other information on results incl. tables

	Test 1	Test2	Test 3	Test 4	Test 5	Test 6
Weightof sample (mg)	149.22	149.22	99.48	99.48	24.87	24.87
Volume n-Octanol saturated water (ml)	18	18	24	24	12	12
Volume water staurated n-Octaniol (ml)	18	18	12	12	24	24
Dilution of n-Octanol layers (ml)	3.33333	3.33333	3.33333	3.33333	3.33333	3.33333
Concentration in n-Octanol phase (mg/l)Detection limit	2.497	2.612	2.727	2.975	1.861	1.629
Concentration in n-Octanol phase allowing for dilution	8.323	8.707	9.09	9.917	6.203	5.43
Number of mg in n-Octanol phase	0.150	0.157	0.109	0.119	0.149	0.130
Dilution of water layers (mls)	1000	1000	500	500	250	250
Concentration in water phase (mg/L)	8.684	8.725	8.289	8.067	8.776	8.672
Concentration in water phase (mg/L) alowing for dilution	8684	8725	4144.5	4033.5	2194	2168
Number of mg in water phase	156.3	157.1	99.5	96.8	26.3	26.0
Number of mg recovered	156.5	157.2	99.6	96.9	26.5	26.1
P= conc in n-octanol/conc in water	0.000960	0.00100	0.00219	0.00246	0.00283	0.00250
Log P	-3.018	-3.00	-2.660	-2.609	-2.548	-2.602
pH of aqueous phase	7.53	7.52	7.27	7.38	7.32	7.18

Applicant's summary and conclusion

Conclusions:

The partition coefficient was determined to be Log P = <-2.7 at 25°C.

Executive summary:

Introduction

The study was intended to determine the partition coefficient and was carried out in accordance with Method A8 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

Results and conclusion

The partition coefficient of the test material has been determined to be Log P =-2.7 at 25°C.