2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethane-1-sulfonyl chloride

Short-term toxicity to aquatic invertebrates

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2018-08-14 to 2018-09-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 202 (Daphnia sp. Acute Immobilisation Test)

Version / remarks:

2004

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Analytical monitoring:

yes

Remarks:

HPLC-DAD

Details on sampling:

- Concentrations: 120 mg/L and 0 mg/L
- Sampling method: At the start of the exposure and at renewal (0 and 24 hours), samples of the fresh media were taken after preparation of the limit concentration and analyzed. At renewal and at the end of the exposure (24 and 48 hours), samples of the 24-hours old media were taken directly from the test vessels and analyzed.
- Sample storage conditions before analysis: no storage

Vehicle:

no

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Method: A limit concentration of 120 mg/L of the test item was prepared with dilution water prior to the start of the exposure (at day 0) and prior to the renewal of the test solution (at day 1). The test item solution was mixed thoroughly by manual agitation.
- Controls: Dilution water without test item incubated under the same conditions as the test groups.
- Evidence of undissolved material (e.g. precipitate, surface film, etc.): No

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Common name: Water flea
- Strain/clone: Daphnia magna STRAUS
- Age of parental stock (mean and range, SD): Less than 24 h old daphnids from a healthy stock were used for the study. Juvenile daphnids were removed from the culture vessels at the latest 24 h before the start of the exposure and discarded. The juveniles born within the following period of max. 24 h preceding the exposure were used for the test. No first brood progeny was used for the test.
- Feeding during test: None

ACCLIMATION
- Acclimation period:Acclimatization of the daphnids was not necessary, because the composition of the dilution water was equivalent to the culture medium

Test type:

semi-static

Water media type:

freshwater

Limit test:

yes

Total exposure duration:

48 h

Hardness:

0h: 259 mg CaCO3/L and 24 h: 263 mg CaCO3/L

Test temperature:

18 - 22 °C, constant within ± 1 °C

pH:

7.48 to 7.75 in fresh media and 7.34 to 7.48 in old media

Dissolved oxygen:

8.77 to 8.90 in fresh media and 7.19 to 8.04 in old media

Conductivity:

0h: 574 µS/cm and 24h: 577 µS/cm

Nominal and measured concentrations:

Nominal: 120 mg/L and 0 mg/L
measured: 0h (fresh medium): 136 mg/L, 24h (old medium): 109 mg/L, 24h (fresh medium): 128 mg/L, 48h (old medium): 116 mg/L, variation was ≤ 20% in each case, thus EC-values are given in nominal concentrations.

Details on test conditions:

TEST SYSTEM
- Test vessel: Beakers
- Type (delete if not applicable): closed, loosely covered with watch glasses
- Renewal rate of test solution (frequency/flow rate): The test solutions were renewed after 24 hours. For this purpose, a second set of test vessels was filled with the freshly prepared test solutions and the daphnids were transferred by pipette
- 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: Culture Medium Elendt M4 according to OECD 202
- Culture medium different from test medium: no

OTHER TEST CONDITIONS
- Adjustment of pH: no
- Photoperiod: 16/8 hours light/dark cycle
- Light intensity: Diffuse light, light intensity of max. 1500 lx

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) : immobilization was determined in all groups after 24 and 48 hours. An animal was considered immobile, if it was not able to swim in the water phase within 15 seconds after gentle agitation of the test vessel. Other adverse effects did not appear.

VEHICLE CONTROL PERFORMED: no

RANGE-FINDING STUDY
- Test concentrations: 1, 10, 100 mg/L
- Results used to determine the conditions for the definitive study: no immobilization occurred

Reference substance (positive control):

yes

Remarks:

potassium dichromate

Key result

Duration:

48 h

Dose descriptor:

EC10

Effect conc.:

> 120 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

> 120 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Key result

Duration:

48 h

Dose descriptor:

EC100

Effect conc.:

> 120 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Details on results:

- Other biological observations: none
- Mortality of control: none
- Other adverse effects control: none
- Any observations (e.g. precipitation) that might cause a difference between measured and nominal values: no

Results with reference substance (positive control):

- Results with reference substance valid? yes
- Relevant effect levels: EC50 (0-24h): 0.6 - 2.4 mg/L acc. 16 AQS P 9/2 (02/2000); Clone 5 and 0.6 - 2.1 mg/L acc. to OECD 202 (2004), Clone A, measured: 2.03 mg/L (1.17 - 3.57 mg/L)

Reported statistics and error estimates:

Methods of evaluation: The effects of the limit concentration were deduced directly from the observed immobilization rates. The effect levels (EC10/ 50/100) are given based on the analytically confirmed nominal concentrations.

Table 1: Measured Concentrations and Percent of Nominal Concentration of the Test item 2H-lsoindole-2-ethanesulfonic acid, 1,3-dihydro-1,3-dioxo-, potassium salt (1:1) (TA-1) during the Definitive Test

Sampling date	0 h fresh medium		24h old medium		24 h fresh medium		48 h old medium
Nominal concentration of the test item [mg/L]	2H-isoindole-2-ethanesulfonic acid, 1,3-dihydro-1,3-dioxo-, potassium salt (1:1) (TA-1)
	Meas. Conc. [mg/L]	%	Meas. Conc. [mg/L]	%	Meas. Conc. [mg/L]	%	Meas. Conc. [mg/L]	%
120	136	113	109	91	128	106	116	97
Control	< LOQ		< LOQ		< LOQ		< LOQ

Validity criteria fulfilled:

yes

Conclusions:

In the limit concentration 120 mg/L of the test item 2H-lsoindole-2-ethanesulfonic acid, 1,3-dihydro~1,3-dioxo-, potassium salt (1:1) (TA-1), no effects on Daphnia magna were observed.

Reference 2

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
For detailed information please refer to the 'attached justification' section

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar biodegradation and ecotoxicological behaviour because the target substance, TA-2, exhibits the same core structure as TA-1 (source substance). TA-2 was investigated for stability in aqueous solutions by implementation of analytical methods via LC-MS/MS and LC-QToF employing ESI ionization. Based on observations resulting from these experiments, a complete hydrolysis of the test item within the mobile phase contact time (less than 1 minute for all experiments) can be assumed. This corresponds to the known reactivity (hydrolytically instability) of the sulfonyl chloride functional group of the target substance. Hydrolysis of 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethane-1-sulfonyl chloride (TA-2) results in its breakdown product 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethane-1-sulfonic acid which is also considered to be the main constituent in aqueous solutions of the source substance 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethane-1-sulfonic acid- potassium (TA-1) . Studies to determine biodegradation and aquatic ecotoxicity are conducted in water, thus, these studies use the hydrolysis product 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethane-1-sulfonic acid as active ingredient. Testing of TA-2 in aqueous solutions is therefore assumed to reveal the same results as compared to TA-1.

2. SOURCE AND TARGET CHEMICAL(S)
The target substance, 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) ethane-1-sulfonyl chloride contains Phthalimid as core structure linked to an ethansulfonyl chloride group. Furthermore, the target substance is hydrolytically not stable and is experimentally shown to rapidly degrade to 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethane-1-sulfonic acid (source substance) and chloride.
The source substance 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethane-1-sulfonic acid--potassium is a water soluble substance for which was shown to be stable in aqueous solutions (study according to OECD guideline 201). It consists of the same core structure as the target substance (Phthalimid with sulfonic acid as functional group). TA-1 as a solid contains potassium as counter ion but when used in aqueous solutions is considered to be present as free sulfonic acid form.

3. ANALOGUE APPROACH JUSTIFICATION
The read-across hypothesis is based on the assumption that 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl) ethane-1-sulfonyl chloride hydrolyses fast to 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethane-1-sulfonic acid. The source substance 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethane-1-sulfonic acid--potassium (TA-1) is considered to be present in the free sulfonic acid form when dissolved in aqueous solutions, thus, the tests on biodegradation and ecotoxicity are performed with the same compound regardless whether TA-1 or TA-2 is used. Furthermore, available physico-chemical data reveal similar properties for both substances supporting the read-across strategy.

4. DATA MATRIX
For detailed information please refer to the 'attached justification' section

Reason / purpose for cross-reference:

read-across source

Key result

Duration:

48 h

Dose descriptor:

EC10

Effect conc.:

> 120 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

> 120 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Key result

Duration:

48 h

Dose descriptor:

EC100

Effect conc.:

> 120 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Validity criteria fulfilled:

yes

Conclusions:

In the limit concentration 120 mg/L of the test item 2H-lsoindole-2-ethanesulfonic acid, 1,3-dihydro~1,3-dioxo-, potassium salt (1:1) (TA-1), no effects on Daphnia magna were observed.
The target substance 2 -(1,3 -dioxo-1,3 -dihydro-2H-isoindol-2 -yl)ethane-1 -sulfonyl chloride (TA-2) is hydrolytically not stable and is experimentally shown to rapidly degrade to 2 -(1,3-dioxo-1,3 -dihydro-2H-isoindol-2 -yl)ethane-1 -sulfonic acid and chloride. The source substance 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethane-1-sulfonic acid--potassium (TA-1) is present in the free sulfonic acid form when dissolved in aqueous solutions, thus, the tests on biodegradation and ecotoxicity are performed with the same compound regardless whether TA-1 or TA-2 is used. Therefore, the results for the source substance apply likewise to the target substance.

Description of key information

For 2 -(1,3 -dioxo-1,3 -dihydro-2H-isoindol-2 -yl)ethane-1 -sulfonyl chloride (TA-2) no experimental study on short-term toxicity to aquatic invertebrates is available.

The target substance 2 -(1,3 -dioxo-1,3 -dihydro-2H-isoindol-2 -yl)ethane-1 -sulfonyl chloride (TA-2) is hydrolytically not stable and is experimentally shown to rapidly degrade to 2 -(1,3 -dioxo-1,3 -dihydro-2H-isoindol-2 -yl)ethane-1 -sulfonic acid and chloride. The source substance 2 -(1,3 -dioxo-1,3 -dihydro-2H-isoindol-2 -yl)ethane-1 -sulfonic acid--potassium (TA-1) is present in the free sulfonic acid form when dissolved in aqueous solutions, thus, the tests on biodegradation and ecotoxicity are performed with the same compound regardless whether TA-1 or TA-2 is used. Therefore, the results for the source substance apply likewise to the target substance.

The 48h-acute toxicity of 2 -(1,3 -dioxo-1,3 -dihydro-2H-isoindol-2 -yl)ethane-1 -sulfonic acid--potassium (TA-1) to Daphnia magna under semi-static conditions with a nominal concentrations of 120 mg/L showed no toxicity for Daphnia magna (48h EC50 > 120 mg/L based on immobilisation).