[ethylenebis[nitrilobis(methylene)]]tetrakisphosphonic acid, calcium sodium salt

Endpoint summary

Additional information

Reliable data are available for EDTMP-xNa for mutagenicity to bacteria, and from in vitro mammalian gene cell mutation assay. Reliable data are available for EDTMP-H from an in vitro cytogenicity study; supporting data are available for EDTMP-H from in vitro bacterial and mammalian mutagenicity studies. Reliable data are available for EDTMP-xCaxNa for mutagenicity to bacteria. Supporting data are available for EDTMP-xK for mutagenicity to bacteria. Reliable data are available for EDTMP-H from an in vivo chromosome aberration study in rat (oral gavage administration).

In dilute aqueous conditions of defined pH, such as the ones in which in vitro studies are conducted, a salt will behave no differently to the parent acid, at identical concentration of the particular speciated form present, and will be fully dissociated to yield EDTMP-H and salt. Hence, genetic toxicity properties for a salt (in contact with water or in aqueous media) can be directly read across to the parent acid and vice versa. In the present context the effect of the alkaline metal counter-ion (sodium) will not be significant and has been extensively discussed in the public literature. In biological systems and the environment, polyvalent metal ions will be present, and the phosphonate ions show very strong affinity to them.

EDTMP-5Na has been tested in a study conducted according to a protocol that is similar to OECD 471 (Monsanto 1981). No evidence of mutagenicity to bacteria was found with or without microsomal activation in Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538. Appropriate positive, negative and solvent controls were included and gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test. The study is considered to be reliability 2.

EDTMP-xCaxNa has been tested according to a protocol that is similar to OECD 471. No increase in the number of revertants was observed when Salmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 were tested up to cytotoxic concentrations with and without metabolic activation (Gridley J., Ross W. D. 1981). Appropriate positive, negative and solvent controls were included and gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test. The study is considered to be reliability 2.

EDTMP-xNa has been tested according to OECD 471 in Salmonella typhimurium strain TA 102 in compliance with GLP (Sokolowski, A (2012)). No increase in the number of revertants was observed with or without activation in either the initial plate incorporation assay or the repeat experiment using pre-incubation. Appropriate positive, solvent and untreated controls were included and gave expected results. It is concluded that the test substance is negative for mutagenicity to bacteria under the conditions of the test.

Further supporting studies for mutagenicity to bacteria are available: EDTMP-H and EDTMP-xK have been tested and shown to be negative for mutagenicity to Salmonella strains TA98, TA100, TA1535, TA1537 and TA1538, with and without metabolic activation (Flowers 1976, Flowers 1977, both reliability 4).

EDTMP-H has been tested according to protocol that is similar to OECD 473 (Li A. P., Myers C. A. 1986). The study was considered to be reliability 2. No test substance induced increase in the incidence of chromosome aberrations in Chinese hamster ovary cells was observed with or without metabolic activation in either Lot A or Lot B. Appropriate solvent and positive controls were included and gave expected results. It is concluded that the test substance is negative for the induction of chromosomal aberrations under the conditions of the test.

EDTMP-xNa has been tested in CHO cells for its potential to induce forward mutation according to a protocol that is similar to OECD 476 and in compliance with GLP (Li A. P. 1986). No evidence of mutagenicity was observed with or without metabolic activation in the initial or the repeat experiments. Appropriate positive and test medium controls were included and gave expected results. It is concluded that the test substance is negative for induction of forward mutations in CHO cells under the conditions of the test.

EDTMP-H has been tested in an in vivo chromosome aberration assay conducted according to a protocol that is similar to OECD 475 and under GLP conditions (EG&G 2001). The substance was administered orally at 0.24, 0.80 and 2.40 mg/kg bw/d to albino Sprague Dawley rats for 5 days. No test substance treatment related mortalities were observed. Appropriate solvent (corn oil), negative (water) and positive controls were included and gave expected results. The test substance did not induce any chromosomal damage in the bone marrow cells of the treated rats. It is concluded that EDTMP-H is negative for the induction of chromosome aberrations in rat bone marrow under the conditions of the study.

Short description of key information:
In vitro:
Gene mutation (Bacterial reverse mutation assay / Ames test): EDTMP-5Na: negative with and without activation in Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 (similar to OECD TG 471) (Gridley J., Ross W. D. 1981a).
Gene mutation (Bacterial reverse mutation assay / Ames test): EDTMP-xCaxNa: negative with and without activation in Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 (similar to OECD TG 471) (Gridley J., Ross W. D. 1981b).
Gene mutation (Bacterial reverse mutation assay / Ames test): EDTMP-xNa: negative with and without activation in Salmonella typhimurium strain TA 102 (OECD TG 471) (Sokolowski, A (2012)).
Cytogenicity in mammalian cells: negative with and without activation in Chinese hamster ovary cells (similar to OECD TG 473) (Li A. P., Myers C. A. 1986).
Mutagenicity in mammalian cells: EDTMP-xNa: negative with and without activation in CHO cells (similar to OECD 473) (Li, A. P. 1986).
In vivo:
Mammalian Bone Marrow Chromosome Aberration Test in rat (oral gavage study): EDTMP-H: negative (similar to OECD TG 475) (EG&G 2001).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available in vitro and in vivo genotoxicity data, EDTMP-xCaxNa is not classified for mutagenicity according to Regulation (EC)1272/2008.