4,4'-bis(diethylamino)benzophenone

Short-term toxicity to fish

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

short-term toxicity to fish

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 August 2017 to 16 October 2017 (experimental period)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

OECD Guideline 203 (Fish, Acute Toxicity Test)

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Analytical monitoring:

yes

Details on sampling:

- Concentrations: Control and all test concentrations
- Sampling method: 2.0 mL from approximate centre of test vessels
- Sample storage conditions before analysis: Stored in a freezer (

Vehicle:

no

Details on test solutions:

PREPARATION AND APPLICATION OF TEST SOLUTION (especially for difficult test substances)
- Method: Test solutions were prepared at nominal 100 mg/L in adjusted ISO medium. Test solutions were stirred for 3 days by magnetic stirrer to ensure maximum dissolution and homogenisation of test substance. After stirring the saturated solution was filtered through 0.45 um membrane filter. Lower test solutions (range-finding only) were prepared by dilution in adjusted ISO medium of the nominal 100 mg/L saturated solution. Test solution preparation was under dimmed light conditions with glassware covered in aluminium foil
- Eluate: Adjusted ISO medium with 180 mg CaCO3 per litre, using RO water
- Differential loading: No
- Controls: Adjusted ISO medium only
- Chemical name of vehicle (organic solvent, emulsifier or dispersant): Not applicable
- Concentration of vehicle in test medium (stock solution and final test solution(s) or suspension(s) including control(s)): Not applicable
- Evidence of undissolved material (e.g. precipitate, surface film, etc.): No

Test organisms (species):

Cyprinus carpio

Details on test organisms:

TEST ORGANISM
- Common name: Carp
- Source: Zodiac, proefacc, 'De Haar Visson', Wageningen University and Research Centre, The Netherlands
- Age at study initiation (mean and range, SD): No data
- Length at study initiation (length definition, mean, range and SD): 2.8 +/-0.3 cm
- Weight at study initiation (mean and range, SD): 0.27 +/-0.07 g
- Method of breeding: F1 from single parent pair
- Maintenance of the brood fish: No data

ACCLIMATION
- Acclimation period: At least 12 days
- Acclimation conditions (same as test or not): Not specified
- Type and amount of food during acclimation: Pelleted fish food (Cyprico Crumble Excellent)
- Feeding frequency during acclimation: Daily
- Health during acclimation (any mortality observed): <5% mortality in 7 days prior to study start

FEEDING DURING TEST
Fish were not fed during the test

Test type:

semi-static

Water media type:

freshwater

Limit test:

yes

Total exposure duration:

96 h

Remarks on exposure duration:

16h daily photoperiod; dimmed light (5 lux)

Hardness:

No data

Test temperature:

21 to 22 oC

pH:

7.5 to 7.9

Dissolved oxygen:

7.1 to 9.2

Salinity:

No data

Conductivity:

No data

Nominal and measured concentrations:

Nominal: 100 mg/L saturated solution
Measured: 0.058 mg/L

Details on test conditions:

TEST SYSTEM
- Test vessel: 6.5 L all glass
- Type (delete if not applicable): open
- Material, size, headspace, fill volume: 4.5 L fill volume
- Aeration: No
- No. of organisms per vessel: 7
- No. of vessels per concentration (replicates): 1
- No. of vessels per control (replicates): 1

TEST MEDIUM / WATER PARAMETERS
- Source/preparation of dilution water: RO water

OTHER TEST CONDITIONS
- Adjustment of pH: No
- Photoperiod: 16h, reduced light (5 lux)
- Light intensity: No data

EFFECT PARAMETERS MEASURED (with observation intervals if applicable) :

TEST CONCENTRATIONS
- Spacing factor for test concentrations: Not applicable
- Range finding study:
- Test concentrations: 1.0, 10 and 100% saturated solution.
- Results used to determine the conditions for the definitive study: Yes

Reference substance (positive control):

no

Duration:

24 h

Dose descriptor:

LC50

Effect conc.:

>= 0.058 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

>= 0.058 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Duration:

72 h

Dose descriptor:

LC50

Effect conc.:

>= 0.058 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

>= 0.058 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Sublethal observations / clinical signs:

Average measured concn (mg/L)	Initial no. of fish	Cumulative mortality					Total mortality (%)
		3h	24h	48h	72h	96h
Control	7	0	0	0	0	0	0
0.058	7	0	0	0	0	0	0

Validity criteria fulfilled:

yes

Conclusions:

The 96-hour LC50 (mortality) for common carp (Cyprinus carpio) was beyond the range tested, ie exceeded the average measured exposure concentration of 0.058 mg/L. The LC50 (mortality) was determined to be >0.058 mg/L under the conditions of the test.

Executive summary:

A 96-hour acute toxicity study with common carp (Cyprinus carpio) was conducted in accordance with the OECD test guideline 203 and in compliance with GLP.

A limit test was performed with a single test concentration of 100% saturated solution of a nominal 100 mg/L solution, under semi-static conditions. The average measured test concentration was determined to be 0.058 mg/L.

Under the conditions of the test, the 96-hour LC50 (mortality) was determined to be >0.058 mg/L, based on average measured concentrations.

This acute toxicity study is considered acceptable and satisfies the guideline requirement for short-term toxicity to fish.

Reference 2

Endpoint:

short-term toxicity to fish

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:

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The following functional groups are common across the target and source substance: aryl groups and carbonyl groups. It is the scientific hypothesis of this read-across justification that the presence of these functional groups dictates the toxicological potential of the target substance. The target and sources substances all pass Lipinski’s rule of five and are therefore considered to have the potential to be absorbed into the body via the oral route. The breakdown products within the body are likely to be similar, or the same, as shown in the table below.
Breakdown products:
Source substance - Benzophenone, Toluene, Hippuric acid or ortho-Cresol
Target substance - Benzophenone, Diethylamine (x2)

The target and source substance are expected to degrade in a similar way within the body and are expected to generate similar if not the same major metabolites. The molecular weight of the target and source substance are similar and are both below 500 daltons. The water solubility and partition coefficients of the target and source substances are comparable.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The source and target substances are composed of the same functional groups bound together in similar ways. The molecular weight of the target and source substances are similar and they are expected to be absorbed in similar ways. The breakdown products of the substance are expected to be the same or very similar and are expected to have the same potential for ecotoxicity.
The target and source substance contains very low levels of unidentified impurities. These impurities are considered not to affect the classification and labelling of the substance due to the very low levels at which they occur. No information on impurities present in the source test materials was available in the literature sources.
The impact of “impurities” is therefore considered not to affect the reliability of the read-across prediction.



3. ANALOGUE APPROACH JUSTIFICATION
Due to the similarities of the source and target substance with regards to physico-chemical properties and the fact that the target substance is expected to breakdown into structurally similar molecules in the aquatic environment, the target substance is expected to behave in a substantially similar manner to the source substance. The target substance is therefore predicted LC50 >0.058 (the limit of water solubility in the study), without mortality observed, in the OECD 203 study when conducted in the Cyprinus carpio. By extension, the target substance is considered not to fulfil the criteria for substances hazardous to the aquatic environment under the Classification, Labelling, and Packaging (CLP) regulation (1272/2008).

4. DATA MATRIX
See appended full justification document.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 203 (Fish, Acute Toxicity Test)

Version / remarks:

1992

Deviations:

no

Key result

Duration:

96 h

Dose descriptor:

LC50

Effect conc.:

0.058 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Duration:

72 h

Dose descriptor:

LC50

Effect conc.:

0.058 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

0.058 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Duration:

24 h

Dose descriptor:

LC50

Effect conc.:

0.058 mg/L

Nominal / measured:

meas. (arithm. mean)

Conc. based on:

test mat.

Basis for effect:

mortality (fish)

Validity criteria fulfilled:

yes

Description of key information

Guideline study conducted to GLP.

Key value for chemical safety assessment

Fresh water fish

Fresh water fish

Dose descriptor:

LC50

Effect concentration:

> 0.058 mg/L