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Additional information

In vitro:

Robbiano et al. (1999) studied an in vitro mammalian cell micronucleus test (method according to Bruggeman et al., 1989). Rat and human kidney cells were used, concentrations ranged from 1800 - 5600 umol, test done without metabolic activation. Trilon AS was positive for both cell types with slight toxicity at the highest dose.

Dunkel et al. (1985) showed a negative result testing Na3NTA.H2O in a bacterial reverse mutation assay. This test was done largely according to OECD guideline 471, concentrations ranged from 3 - 3333 ug/plate with and without metabolic activation.

Zeiger et al. (1992) also found a negative result testing Na3NTA.H2O in a bacterial reverse mutation assay. Concentrations ranged from 33 - 2000 ug/plate, tested with and without metabolic activation. This test was done also largely according to OECD guideline 471.

A cell transformation test with Trilon AS showed a positive result, when tested in concentrations up to > 10 mM with Syrian hamster embryo cells (LeBoeuf, 1996). Testing was done without metabolic activation.

Caspary et al. (1988) showed a negative result with Na3NTA.H2O in a mouse lymphoma assay using L5178Y cells with and without metabolic activation. Test concentrations were 1000 - 3000 ug/ml.

A sister chromatid exchange assay in mammalian cells was negative when tested without metabolic activation with CHO cells. Concentrations used were 0.001 - 2 mM of Trilon A (Montaldi et al., 1985).

Celotti et al. (1987) tested V79 Chinese hamster cells with and without metabolic activation in a mammalian cell gene mutation assay. Negative results were obtained using Na3NTA in concentrations of 0.1 - 15 mM.

Montaldi (1985) reported a negative result for Trilon A in a sister chromatid exchange assay in mammalian cells, Nakatsuka (1990) found a positive result in a mammalian cell gene mutation assay with Fe+-NTA and a negative result with Fe+NTA in a mammalian chromosome aberration test, Lanfranchi reported a negative result for Na3NTA in a cell transformation assay, Traul (1981) showed a positive result in a cell transformation assay wtih Trilon A, Miltenburger (1995) reported a positive result in a mammalian abberation test with Trilon A and DeMarco (1986) found a positive result in a mammalian chromosome aberration assay with Trilon A.

In vivo:

With Trilon AS, inconclusive results were reported when tested oral and i.v. in a micronucleus assay (Robbiano, 1999). Male rats were given the test substance i.v. in a concentration of 250 mg/kg and a single p.o. administration of 1/2 of the LD50 performed 2 days after folic acid injection or as three p.o. administrations of 1/3 of the LD50 during the 3 days after folic acid injection. In both cases, rats were euthanized 4 days after folic acid treatment.

A micronucleus test according to OECD guideline 474 with Trilon A reported negative results when using doses of 500, 1000 and 2000 mg/kg. The test substance was given twice orally (gavage), male mice were used for this test (BASF, 2004).

A mammalian germ cell cytogenetic assay was done with Trilon A using male mice (BASF, 2000). The test substance was given orally (gavage) in doses of 100, 330 and 1000 mg/kg. Negative results were found.


Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Classification:

Most of the above mentioned studies showed negative results (in vitro as well as in vivo). Classification regarding mutagenicity is not warranted.