1,2-Benzenediol, 4-[(4-methylphenyl)sulfonyl]-

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:

(Q)SAR

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE
ECOSAR

2. MODEL (incl. version number)
ECOSAR v1.11

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
c1(O)c(O)cc(S(=O)(=O)c2ccc(C)cc2)cc1


4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
[Explain how the model fulfils the OECD principles for (Q)SAR model validation. Consider attaching the QMRF or providing a link]
See QMRF

5. APPLICABILITY DOMAIN
[Explain how the substance falls within the applicability domain of the model]
See QPRF

6. ADEQUACY OF THE RESULT
[Explain how the prediction fits the purpose of classification and labelling and/or risk assessment]

Qualifier:

according to guideline

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

ECOSAR™ Version 1.11 (Sept 2012): The Ecological Structure Activity Relationships (ECOSAR) Class Program estimates the aquatic toxicity of industrial chemicals. The program estimates acute (short-term) toxicity and chronic (long-term or delayed) toxicity to aquatic organisms to fish, aquatic invertebrates, and green algae, and has limited SARs for other salt water and terrestrial species, where data were available. This program is maintained by a separate division in the Agency

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

70.708 mg/L

Remarks on result:

other: Phenols

 

ECOSAR class	Organism	Duration	EndPt	Predicted (mg/L)
Phenols, Poly	Daphnid	48 hr	LC50	70.708

 

Validity criteria fulfilled:

not applicable

Conclusions:

Depending on the ECOSAR class of the substance the LC50 is predicted to be around 70.708 mg/L.

Executive summary:

QPRF: ECOSAR v1.11 (20 May 2014)

 

1.	Substance	See “Test material identity”
2.	General information
2.1	Date of QPRF	See “Data Source (Reference)”
2.2	QPRF author and contact details	See “Data Source (Reference)”
3.	Prediction
3.1	Endpoint (OECD Principle 1)	Endpoint	Ecotoxicity LC50 48h daphnid
3.2	Algorithm (OECD Principle 2)	Model or submodel name	ECOSAR
		Model version	v. 1.11
		Predicted value (model result)	See “Results and discussion”
		Input for prediction	Chemical structure via CAS number
		Descriptor values	Class specific Estimations
3.3	Applicability domain (OECD principle 3)	Domains:
		Phenols, Poly:              max MW: 1000 g/mol              Max Kow: 5.0 On-Line ECOSAR User’s Guide		Substance within range (264.30 g/mol and estimated Log Kow 2.194) LC50 does not exceed the water solubility by 10x
3.4	The uncertainty of the prediction (OECD principle 4)	Statistical accuracy for training dataset: Phenols, Poly: N=5+6 r² = 0.86
3.5	The chemical mechanisms according to the model underpinning the predicted result (OECD principle 5)	The model largely relies on logKow, which typically is the main descriptor: log P is linked to the partitioning of the substance from water into the lipid phase of the daphnid organism, thus reflecting the chemical bioavailability.

 

 

 

Assessment of estimation domain:

 

Class	Applicability domain limits	Substance parameters
Phenols, Poly	Max MW: 1000 g/mol Max Kow: 5.0	249.29 g/mol estimated Kow 2.152

 

Reference 2

Endpoint:

short-term toxicity to aquatic invertebrates

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2020

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:

Adopted April 13, 2004

Deviations:

no

GLP compliance:

yes

Analytical monitoring:

yes

Details on sampling:

- Concentrations: At the end of the exposure period, the replicates were pooled at each concentration before sampling.
- Sampling method:
Frequency at t=0 h and t=48 h
Volume 4.0 mL from the approximate centre of the test vessels
- Sample storage conditions before analysis: Samples were stored in a freezer (≤-15°C) until analysis at the analytical laboratory of the Test Facility.

Vehicle:

no

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
The batch of CH03951 tested was an off-white powder with a purity of approximately 96.85 w/w%. No correction was made for the purity/composition of the test item.
Preparation of test solutions started with a loading rate of 100 mg/L applying a fifteen-minute period of ultrasonic waves followed by a three-day period of magnetic stirring to ensure maximum dissolution of the test item in test medium. Thereafter, the aqueous Saturated Solution (SS) was collected by filtration through a 0.45 µm membrane filter (RC55, Whatman) and used as the highest test concentration. Lower test concentrations were prepared by subsequent dilutions of the SS in test medium. All test solutions were clear and colorless at the end of the preparation procedure.

Test organisms (species):

Daphnia magna

Details on test organisms:

TEST ORGANISM
- Common name: Water flea
- Strain/clone: In-house laboratory culture with a known history.
- Justification for species other than prescribed by test guideline: This system has been selected as an internationally accepted invertebrate species.
- Source: In-house laboratory culture with a known history.
- Age of parental stock (mean and range, SD): Daphnids originated from a healthy stock, 2nd to 5th brood, showing no signs of stress such as mortality >20%, presence of males, ephippia or discoloured animals and there was no delay in the production of the first brood. Maximum age of cultures: 4 weeks.
- Feeding during test: no
- Food type: /
- Amount: /
- Frequency: Daily, a suspension of fresh water algae.

ACCLIMATION
- Acclimation conditions (same as test or not): same as test
- Type and amount of food: Daily, a suspension of fresh water algae

Test type:

static

Water media type:

freshwater

Limit test:

yes

Total exposure duration:

48 h

Test temperature:

The temperature continuously measured in a temperature control vessel varied between 19 and 20°C during the test and complied with the requirements as laid down in the study plan (18 22°C, constant within ±1°C).

pH:

7.9-8.0

Dissolved oxygen:

8.7-9.7 mg/L

Nominal and measured concentrations:

The measured concentrations at the start of the test were 9.9, 18, 31, 53 and 97 mg/L, respectively.
During the exposure period, the concentrations remained stable, i.e. were at 95-102% relative to the initial concentrations at the end of the test. It was concluded that the undissolved fraction removed during the preparation of test solutions had not been test item related.

Details on test conditions:

TEST SYSTEM
- Test vessel: 60 mL, all-glass
- Type (delete if not applicable): static
- Aeration: No aeration of the test solutions.
- No. of organisms per vessel: 5 per vessel containing 50 mL of test solution
- No. of vessels per concentration (replicates): four replicates
- No. of vessels per control (replicates): 4

TEST MEDIUM / WATER PARAMETERS
M7, as prescribed by Dr. Elendt-Schneider (Elendt, B.-P., 1990: Selenium deficiency in Crustacea. An ultrastructural approach to antennal damage in Daphnia magna Straus. Protoplasma 154, 25-33).

Composition of medium M7:
The following salts (analytical grade) were added to tap water purified by Reverse Osmosis (RO-water, GEON Waterbehandeling, Berkel-Enschot, The Netherlands):
CaCl2.2H2O 211.5 mg/L
MgSO4.7H2O 88.8 mg/L
NaHCO3 46.7 mg/L
KCl 4.2 mg/L
The hardness of test medium expressed as CaCO3: 180 mg/L with a pH between 6 and 9.

OTHER TEST CONDITIONS
- Adjustment of pH: no
- Photoperiod: A daily photoperiod of 16 hours.
- Light intensity: not specified

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :
Immobility (including mortality) At 24 hours and at 48 hours.
pH and Dissolved oxygen At the beginning and at the end of the test, for the highest concentration and the control.
Temperature of medium Continuously in a temperature control vessel, beginning at the start of the test.


VEHICLE CONTROL PERFORMED: yes (medium)

RANGE-FINDING STUDY
- Test concentrations: 0.10, 1.0 and 10% of the SS prepared at a loading rate of 100 mg/L
- Results used to determine the conditions for the definitive study: A final test was performed based on the results of a preceding combined limit/range-finding test.

Reference substance (positive control):

yes

Remarks:

potassium dichromate

Duration:

24 h

Dose descriptor:

EC50

Effect conc.:

49 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: 95% C.I.: 16-20 mg/L

Key result

Duration:

48 h

Dose descriptor:

EC50

Effect conc.:

18 mg/L

Nominal / measured:

nominal

Conc. based on:

test mat.

Basis for effect:

mobility

Remarks on result:

other: 95% C.I.: 16-20 mg/L

Details on results:

No immobility was observed in the control and the lowest test concentration throughout the exposure period. At the four highest test concentrations, a concentration-related increase of immobility was observed with increasing test concentration resulting in 50% immobility at nominally 18 mg/L and 100% immobility at nominally 32 mg/L and above at the end of the test.

Results with reference substance (positive control):

The 24h-EC50 in this reference test with K2Cr2O7 was within the expected range of 0.6 and 2.1 mg/L as specified in ISO International Standard 6341, October 2012. The 48h-EC50 was within the expected range of 0.28 and 0.59 mg/L, as based on reference tests performed with K2Cr2O7 at the Test Facility during the last ten years.
The 24h-EC50 was 0.96 mg/L with a 95% confidence interval between 0.87 and 1.1 mg/L.
The 48h-EC50 was 0.53 mg/L with a 95% confidence interval between 0.47 and 0.53 mg/L.

Reported statistics and error estimates:

See table below for statistics

Parameter	CH03951 Nominal conc. (mg/L)	95%-confidence interval (mg/L)
24h-EC50	49	42-56
48h-EC50	18	16-20

Validity criteria fulfilled:

yes

Conclusions:

In conclusion, the 48h-EC50 for Daphnia magna exposed to CH03951 was 18 mg/L based on analytically confirmed nominal concentrations (95% confidence interval between 16 and 20 mg/L).

Executive summary:

The objective of the study was to evaluate CH03951 for its ability to generate acute toxic effects on the mobility of Daphnia magna during an exposure period of 48 hours and, if possible, to determine the EC₅₀ at 24 and 48 hours of exposure.

A full test was performed based on the results of a combined limit/range-finding test. The study met the acceptability criteria prescribed by the study plan and was considered valid. Test conditions and results of the final test are presented in the table below:

Test Item:	CH03951
Appearance:	Off white powder
Purity:	Approximately 96.85 w/w%
Preparation of test solutions:	Saturated Solution (SS), loading rate of 100 mg/L. Lower concentrations: serial dilution.
Experimental Set-up
Guideline(s)	OECD TG 202 (2004) and OECD GD 23 (2019)
Exposure design:	Static, no renewals
Test concentration(s):	Solutions containing 10, 18, 32, 56 and 100% of the SS
Control	Blank control
Number of replicates	4 replicates containing 5 daphnids each
Sampling for analysis	At t=0 and 48 hours
Experimental conditions
pH, Temperature, Dissolved Oxygen	Within the ranges specified in OECD TG 202
Light regime	A daily photoperiod of 16 hours
Results
Actual exposure concentrations	10, 18, 32, 56 and 100 mg/L (analytically confirmed nominal concentrations)
Recorded effects	No immobility was observed in the control and the lowest test concentration throughout the exposure period. At the four highest test concentrations, a concentration-related increase of immobility was observed with increasing test concentration resulting in 50% immobility at nominally 18 mg/L and 100% immobility at nominally 32 mg/L and above at the end of the test.
Effect parameters

Parameter	CH03951 Nominal conc. (mg/L)	95%-confidence interval (mg/L)
24h-EC50	49	42-56
48h-EC50	18	16-20

Description of key information

Based on read-across from a structural analogue, the EC50 for short-term toxicity to aquatic invertebrates was set at 19.1 mg/L.

Key value for chemical safety assessment

Fresh water invertebrates

Fresh water invertebrates

Effect concentration:

19.1 mg/L