Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study planned
Study period:
After approval by ECHA
Justification for type of information:
TESTING PROPOSAL ON VERTEBRATE ANIMALS
STATEMENT REGARDING STEPWISE ASSESSMENT AND TESTING

The registered substance, HMDTMP (4-7Na) (Sodium salts of {hexane-1,6-diylbis[nitrilobis(methylene)]}tetrakisphosphonic acid (4-7:1); No EC yet) is a member of a group of analogous aminomethylenephosphonate and other organophosphonate substances and within this group there are some existing studies available for the sub-chronic oral repeated dose toxicity endpoint (guideline compliant or similar standard; gavage or dietary exposure; duration 90 days to 1 year; in rats). Therefore, before proceeding with any OECD 408 study, the registrant (as a member of the Phosphonates Consortium) proposes a strategy to examine the case for read-across to fulfil this REACH required endpoint, using in vitro testing as supporting evidence as part of a decision-making framework. In view of limited laboratory capacity at the present time it has not been possible to initiate any work as yet.

It may be the case that an appropriate read-across of a specific existing reliable study within this analogue group is sufficiently well justified, or that a weight-of-evidence approach is shown to be appropriate based on read-across data across the group. In this situation, the Registrant will update the dossier without delay to include such read-across data with justification to support the read-across, and the testing proposed herein will then no longer be required.

NON-CONFIDENTIAL NAME OF SUBSTANCE:
- Name of the substance on which testing is proposed to be carried out: It is proposed to perform the study with the related substance, HMDTMP (4-7K) (Potassium salts of {hexane-1,6-diylbis[nitrilobis(methylene)]}tetrakisphosphonic acid (4-7:1); EC 701-184-1).
- Name of the substance for which the testing proposal will be used: The registered substance and Potassium salts of {hexane-1,6-diylbis[nitrilobis(methylene)]}tetrakisphosphonic acid (4-7:1); EC 701-184-1.
CONSIDERATIONS THAT THE GENERAL ADAPTATION POSSIBILITIES OF ANNEX XI OF THE REACH REGULATION ARE NOT ADEQUATE TO GENERATE THE NECESSARY INFORMATION:
- Available GLP studies: none for repeated dose toxicity endpoint for the registered substance. However, data are available within the analogue group of aminomethylenephosphonate and other organophosphonate substances. Refer to the Data Matrix attached in Section 13 of the dossier.
- Available non-GLP studies: none for repeated dose toxicity endpoint for the registered substance. However, data are available within the analogue group of aminomethylenephosphonate and other organophosphonate substances. Refer to the Data Matrix attached in Section 13 of the dossier.
- Historical human data: no data
- (Q)SAR: no data
- In vitro methods: no validated alternative in vitro methods are available
- Weight of evidence: insufficient data at the present time
- Grouping and read-across: Please refer to the Statement regarding stepwise assessment and testing (above).
CONSIDERATIONS THAT THE SPECIFIC ADAPTATION POSSIBILITIES OF ANNEXES VI TO X (AND COLUMN 2 THEREOF) OF THE REACH REGULATION ARE NOT ADEQUATE TO GENER ATE THE NECESSARY INFORMATION:
- None of Column 2 adaptations for repeated dose toxicity applies to HMDTMP category.
Repeated dose toxicity: oral study proposal
FURTHER INFORMATION ON TESTING PROPOSAL IN ADDITION TO INFORMATION PROVIDED IN THE MATERIALS AND METHODS SECTION:
- a Repeated Dose 90-Day Oral Toxicity Study in Rodents (OECD 408) will be conducted with the analogous substance, HMDTMP (4-7K) (Potassium salts of {hexane-1,6-diylbis[nitrilobis(methylene)]}tetrakisphosphonic acid (4-7:1); EC 701-184-1), only in the event that no read-across from existing available reliable studies is possible.

The OECD 408 study is an IX Annex study, while the registered substance is Annex VIII. However, to avoid unncessary testing of vertebrate animals, it seems appropriate to read-across the higher Annex OECD 408 study rather than conducting an additional OECD 422 lower Annex study.

Data source

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat

Results and discussion

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion