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

Short-term toxicity to aquatic invertebrates

Administrative data

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The experimental start and completion dates were 24 and 27 May 2011. The report was issued 04 August 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:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Deviations:

yes

Remarks:

Test solutions prepared in dechlorinated water

GLP compliance:

yes

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

Sampling and analysis

Analytical monitoring:

yes

Details on sampling:

- Concentrations: 120 mg/L test substance (nominal)
- Sampling method; Samples taken at 0h from excess test solutions. Samples at 48h taken from single test replicate and analysed post centrifugation.

Test solutions

Vehicle:

no

Test organisms

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Common name: Daphnia sp.
- Source: Continuous laboratory culture at Brixham Environmental Laboratory
- Age at study initiation: <24h
- Method of breeding: diploid parthogenesis
- Feeding during test: none

Study design

Test type:

static

Water media type:

freshwater

Limit test:

yes

Total exposure duration:

48 h

Test conditions

Hardness:

50 mg/L CaCO3

Test temperature:

20.6-20.7 degrees centigrade

pH:

8.0-8.4

Dissolved oxygen:

8.2-8.4 mg/L (90-93% of air saturation value)

Salinity:

not applicable

Nominal and measured concentrations:

Test concentrations were dechlorinated medium control and nominal concentrations of 120 mg/L (nominal) test substance. The measured concentration in the nominal 120 mg/L was 100% of nominal at the start of the test and 20% of nominal at the end. On the basis of the analytical data the geometric mean measured concentration was used for calculating and reporting of the results.

Details on test conditions:

TEST SYSTEM
- Test vessel: 250ml glass beakers
- Material, size, headspace, fill volume: 200ml of test solution providing a depth of approx 60mm
- Aeration: none
- No. of organisms per vessel:5
- No. of vessels per concentration (replicates):4
- No. of vessels per control (replicates):4

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: dechlorinated water aerated overnight
- Conductivity: 201uS/cm

- Photoperiod: 16h light and 8h dark with 20 min. dusk/dawn transition

EFFECT PARAMETER MEASURED: Observations at 24h and 48h of whole body movement. Absence of movement in a 15s period is considered immobile

Reference substance (positive control):

no

Results and discussion

Effect concentrations

Effect concentrations 1

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

> 54 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

mobility

Effect concentrations 2

Key result

Duration:

48 h

Dose descriptor:

NOEC

Effect conc.:

54 mg/L

Nominal / measured:

meas. (geom. mean)

Conc. based on:

test mat.

Basis for effect:

mobility

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

It is concluded that as none of the Daphnia magna were observed as immobilised after 24 or 48h in the control or test concentration solutions and no other symptoms of toxicity were observed that the test substance has no toxic effect on Daphnia magna at 54 mg/L (based on geometric mean measured concentrations).

Executive summary:

Introduction.

A study was performed to assess the acute toxicity of the test material to Daphnia magna. The method followed that described in the OECD Guidelines for Testing of Chemicals (April 2004) No 202, "Daphnia sp, Acute Immobilisation Test" referenced as Method C.2 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

Methods.

This study was run with a control and nominal test substance concentration of 120 mg/L. The number of immobilised Daphnia were recorded after 24 and 48 hours.

Results and Conclusion

The 48 -hour EC50 for the test material to Daphnia magna based on nominal test concentration was greater than 54 mg/L. The No Observed Effect Concentration (NOEC) is defined as the highest tested concentration in which there was no immobility observed within the period of the test and is derived directly from the test observations. Therefore, the 48 hour NOEC was determined to be 54 mg/L. There was no immobility observed in the control.