Registration Dossier

Administrative data

Key value for chemical safety assessment

Additional information

Information is available for DTPMT acid from bacterial and mammalian mutagenicity studies, and from an in vivo chromosome aberration study in rats. Information is available from in vitro cytogenictity studies on the related substance, DTPMP-xNa. The results of all the bacterial mutagenicty studies were negative. The key study was selected on the basis of reliability. Results from mammalian mutagenicity studies were conflicting: in L5178Ycells, mutagenic effects were observed, and appeared to be unrelated to pH, but the results were not reproduced when DTPMP acid was tested in Chinese hamster ovary cells (HPGRT locus). The negative result was selected as key as it is considered to reflect the properties of the substance. Evidence for potential to induce chromosome aberrations in vitro from a study on the related substance are not supported by the negative results from an in vivo study on DTPMP acid.

It is probable that the positive response for DTPMP acid does not reflect an ability to interact with DNA due to (1) lack of structural alerts for mutagenicity, (2) lack of evidence for gene mutation potential in sub-mammalian systems and (3) lack of potential to induce gene mutations in another well-conducted assay investigating mutations at the hprt locus in CHO cells. One known artefact of the assay (perturbation of pH) was excluded experimentally. Whilst osmolarity was not assessed in the studies on DTPMP acid, it is an unlikely cause of the positive response due to the low concentration at which a positive response on the acid was seen (0.73 mM) and because positive responses are only seen consistently in the presence of S9. These substances are strong chelators and there is some unpublished evidence that other chelators produce positive responses in this assay, presumably due to the removal of essential metal ions such as Zn, Mg etc.

Short description of key information:
In vitro:
Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without activation in Salmonella typhimurium TA98, TA100, TA 1535, TA 1538 and E. coli WP2 uvrA (OECD TG 471)
Cytogenicity in mammalian cells: positive in Chinese hamster lung IU cells (OECD TG 473)
Mutagenicity in mammalian cells: negative in L5278Y cells (similar to OECD TG 476)
In vivo:
Bone marrow chromosome study in rats (oral gavage administration): Read-across from DTPMP acid: Negative (similar to OECD TG 475)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The in vitro evidence for mutagenicity is not supported by the in vivo result available. It is therefore considered that non-classification is justified.