2-phosphonobutane-1,2,4-tricarboxylic acid

Long-term toxicity to fish

Administrative data

Endpoint:

fish early-life stage toxicity

Type of information:

experimental study planned (based on read-across)

Justification for type of information:

CONDITIONAL TESTING PROPOSAL ON VERTEBRATE ANIMALS

GENERAL CONSIDERATIONS
A testing proposal for Annex IX Long Term Fish is included in the dossier based on BoA decisions A-010-2018 and A-011-2018. The BoA in A-011/2018 came to the conclusion that registrants are required to propose long-term fish testing under Annex IX in any case, and that registrants may be required to perform / shall propose (under column 2) longer term fish toxicity tests that go beyond those described in Annex IX, column 1. According to the BoA, Annex IX (section 9.1, column 2) does not allow registrants to omit information on long term toxicity to fish under column 1. Rather, according to the BoA, Annex IX requires registrants to submit information on a further study than one of the three listed in Column 1 of Section 9.1.6. of Annex IX, if the chemical safety assessment indicates that it is necessary to investigate the effects of a substance on aquatic organisms beyond what any one of those three Column 1 studies would do.
Our CSA demonstrates PEC/PNEC values of < 1 in all cases. In conclusion, further testing is not warranted. However, a long-term fish study (OECD 210) is nevertheless proposed based on the BoA decision. As the BoA decision A-010-2018 is currently being challenged before the General Court (T-656/20), we respectfully request ECHA to suspend any decision on the testing proposal and to first await the decision of the General Court in the aforementioned case. Vertebrate studies should always be the last resort to generate information. In this regard, reference is made to Para. 132 of C-471/18 P:
“It follows from those general provisions, which are to be construed in the light of recital 47 of the REACH Regulation, according to which it is necessary to replace, reduce or refine testing on vertebrate animals’, that a registrant has, generally and therefore especially where ECHA issues it with a decision asking it to complete its registration dossier with a study involving animal testing, not simply the possibility but the obligation to generate information obtained by means other than animal testing ‘whenever possible’ and to undertake such testing ‘only as a last resort’.”
Case T-656/20 is still ongoing and the decision if long-term fish tests must always be performed is, thus, still not finally decided. In conclusion, LANXESS requests ECHA to not issue any draft decision until the BoA decision’s in case A-010-2018 is upheld by the General Court in case T-656/20, also taking animal-welfare considerations into account.

NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Name of the substance on which testing is proposed to be carried out: Tetrasodium hydrogen 2-phosphonatobutane-1,2,4-tricarbolxyate, CAS No. 66669-53-2, EC No. 266-442-3.
- Name of the substance for which the testing proposal will be used [if different from tested substance]: 2-Phosphonobutane-1,2,4-tricarboxylic acid, CAS No. 37971-36-1, EC No. 253-733-5.

CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- Available GLP studies: Acute toxicity studies are available for fish and algae. In addition, a chronic daphnia study is available. A 14 d Prolonged toxicity test according to OECD 204 is available for the substance. The test shows no effects on Danio rerio after 14 d up to the highest tested concentration of 1042 mg/L. However, as the test does not cover the most sensitive stage in larval development of the test species, it cannot be used to fill the data gap for a chronic fish test.
There are no GLP-compliant fish early-life stage studies available on the substance itself or its structural analogue tetrasodium hydrogen 2-phosphonatobutane-1,2,4-tricarboxylateic acid, CAS No. 66669-53-2, EC No. 266-442-3.
- Available non-GLP studies: There are no non-GLP-compliant fish early-life stage studies available on the substance.
- Historical human data: Not relevant for this endpoint.
- (Q)SAR: There are no QSAR models available for this higher tier ecotoxicological endpoint that are sufficiently validated and acceptable (according to OECD Q/SAR validation criteria).
- In vitro methods: The registrant is not aware of any validated alternative tests that use in vitro methodologies that could be used to meet the standard requirement of the REACH regulation for fish early-life stage toxicity.
- Weight of evidence: No data are available for use in a weight of evidence approach.
- Grouping and read-across: Grouping and read-across approaches have been evaluated.
No studies suitable for read-across or grouping are available. 2-Phosphonobutane-1,2,4-tricarboxylic acid will dissociate in aqueous solution under pH 4-9 as indicated by the pKa values to hydrogen 2-phosphonatobutane-1,2,4-tricarboxylate. It is reasonable to perform the testing with the tetrasodium hydrogen 2-phosphonatobutane-1,2,4-tricarboxylate as the resulting data will be used to fill data gaps for the substance itself and can be used in a read-across approach for 2-phosphonatobutane-1,2,4-tricarboxylic acid. Tetrasodium hydrogen 2-phosphonatobutane-1,2,4-tricarboxylate is slightly easier to handle being available as a solid. Furthermore, it can be assumed, that using the tetrasodium salt will simplify any adjustments to the pH-value, as the salt will not react strongly acidic or basic during dissolution.
- Substance-tailored exposure driven testing [if applicable] : Not applicable
- Approaches in addition to above [if applicable] : Not applicable
- Other reasons [if applicable] : 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:
- Please refer to first section of this testing proposal.
Additional information: Literature searches have been performed in 2020 to find valid data on long-term toxicity to fish for the registered substance. No information sufficient to cover the endpoint could be retrieved.

FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:

- Details on study design / methodology proposed [if relevant]: not relevant

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Tetrasodium hydrogen 2-phosphonatobutane-1,2,4-tricarboxylate

EC Number:

266-442-3

EC Name:

Tetrasodium hydrogen 2-phosphonatobutane-1,2,4-tricarboxylate

Cas Number:

66669-53-2

Molecular formula:

C7H7Na4O9P

IUPAC Name:

hydrogen tetrasodium 2-phosphonatobutane-1,2,4-tricarboxylate

Details on test material:

generic test material

Specific details on test material used for the study:

Test material with high purity will be used