1,4-bis[[4-(1,1-dimethylethyl)phenyl]amino]-5,8-dihydroxyanthraquinone

Long-term toxicity to fish

Administrative data

Endpoint:

fish early-life stage toxicity

Type of information:

experimental study planned

Justification for type of information:

TESTING PROPOSAL ON VERTEBRATE ANIMALS
Short-term toxicity testing on fish is an information requirement under Annex VIII to REACH (Section 9.1.3.). Long-term toxicity testing on fish must be considered (Section 9.1.3., Column 2) if the substance is poorly water soluble. Poorly water soluble substances require longer time to reach steady-state conditions. As a result, the short-term tests do not give a true measure of toxicity for this type of substances and the long-term test is required. A substance is regarded as poorly water soluble if, for instance, it has a water solubility below 1 mg/L or below the detection limit of the analytical method of the test material (ECHA Guidance R.7.8.5).
All substances included in the category approach are poorly water soluble (see the category approach document for further details). Therefore, information on long-term toxicity on fish must be provided in the category to support the read-across and show a trend to assess the aquatic toxicity of these substances. Hence, a testing proposal is included in the present dossier to conduct a Fish Early-Life Stage Toxicity test, according to OECD Test Guideline 210.

NON-CONFIDENTIAL NAME OF SUBSTANCE: C. I. Solvent Green 28

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION :
- Available GLP studies : No data/ no GLP studies are available for Solvent Green 28. Another testing proposal (OECD TG 210) is on-going for Solvent Green 3 (CAS 128-80-3), another member of the anthraquinone category.
- Available non-GLP studies: No data/no studies are available for Solvent Green 28.
- Historical human/control data: No historical human/control data are available.
- (Q)SAR: Due to the possible different MechoA of Solvent Green 28 compared to the five other substances of the category, HA-QSAR predictions using iSafeRat QSAR models cannot be provided for this substance at the time being. Therefore, performing new experimental test on Solvent Green 28 is needed to fulfil chronic fish endpoint.
QSAR data are available only for the five other members of the anthraquinone category:
Solvent Violet 36: 32d-EC10 (fish) > solubility limit*
Solvent Green 3 : 32d-EC10 (fish) > solubility limit*
Reinblau RLW: 32d-EC10 (fish) > solubility limit*
Reinblau BLW: 32d-EC10 (fish) > solubility limit*
Solvent Blue 104# : 32d-EC10 (fish) > solubility limit*
# not registered by LANXESS
* iSafeRat® High Accuracy QSAR predictions (KREATiS, 2022)
- In vitro methods : Not applicable, no valid in vitro methods are available and cannot be used instead of a long term fish test.
- Weight of evidence: No data are available.
- Grouping and read-across: Solvent Green 28 is a member of the anthraquinone category (see category justification document in section 14).
All substances included in the category approach are poorly water soluble with high adsorption coefficient (log Koc > 6), high partition coefficient (log Kow > 8) and not readily biodegradable. These properties lead to a reduced bioavailability for organisms and persistence. As the available short-term tests do not give a true measure of toxicity for these substances, long-term toxicity data are required. To fulfil this chronic endpoint, HA-QSAR predictions, experimental studies and testing fish for long-term exposure are available/requested.
Regarding HA-QSAR predictions, iSafeRat QSAR models were used to calculate the chronic toxicity to fish, for Reinblau RLW, Reinblau BLW, Solvent Violet 36, Solvent Green 3 and Solvent Blue 104. The chronic toxicity of all substances were predicted as greater than the water solubility limit i.e. there would be no toxicological effect.
Then, due to the possible different MechoA of Solvent Green 28 compared to the five other substances of the category, HA-QSAR predictions using iSafeRat QSAR models cannot be provided for this substance at the time being. Therefore, performing new experimental test on Solvent Green 28 is needed to fulfil fish chronic endpoint.
- Substance-tailored exposure driven testing: Not applicable
- Approaches in addition to above : Not applicable
- Other reasons : Not applicable

CONSIDERATIONS THAT THE SPECIFIC ADAPTATION POSSIBILITIES OF ANNEXES VI TO X (AND COLUMN 2 THEREOF) OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
Under Annex VIII, Section 9.1.3., Column 2 of REACH, the long-term aquatic toxicity study on fish shall be considered if the substance is poorly water soluble. Here, as all substances included in the category approach are poorly water soluble, long-term aquatic toxicity data on fish, requested in the Annex IX, Section 9.1.6, Column 1, is needed.

FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
- Details on study design / methodology proposed:
The proposed Fish, Early-Life Stage Toxicity Test (test method: OECD TG 210) is appropriate to cover the information requirement for long-term toxicity on fish (ECHA Guidance R.7.8.4.1.). The chosen substance is difficult to test due to the low water solubility (< 3 μg/L at 20°C) and a high adsorptive property (log Kow of 10.7). OECD TG 210 specifies that for difficult to test substances OECD GD 23 must be followed. Due to the properties of the substance, it may be difficult to achieve and maintain the desired exposure concentrations. Therefore, if the testing proposal is accepted, we will monitor the test concentration(s) of the substance throughout the exposure duration and report the results. If it is not possible to demonstrate the stability of exposure concentrations (i.e. measured concentration(s) not within 80-120% of the nominal concentration(s)), we will express the effect concentration based on measured values as described in OECD TG 210. In case a dose- response relationship cannot be established (no observed effects), we will demonstrate that the approach used to prepare test solutions was adequate to maximise the concentration of the substance in the test solutions.

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 210 (Fish, Early-Life Stage Toxicity Test)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,4-bis[[4-(1,1-dimethylethyl)phenyl]amino]-5,8-dihydroxyanthraquinone

EC Number:

225-443-9

EC Name:

1,4-bis[[4-(1,1-dimethylethyl)phenyl]amino]-5,8-dihydroxyanthraquinone

Cas Number:

4851-50-7

Molecular formula:

C34H34N2O4

IUPAC Name:

1,4-bis[(4-tert-butylphenyl)amino]-5,8-dihydroxy-9,10-dihydroanthracene-9,10-dione

Test material form:

solid

Details on test material:

To be confirmed (testing proposal)