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The ability of Reaction Mass of Lanthanum Phosphate and Cerium Phosphate and Terbium Phosphate to induce genetic damage was assessed in three in-vitro studies. All these studies performed according to OECD guidelines and in compliance with GLP, were scored as validity 1 according to Klimisch criteria and were thus considered as Key studies.

In a bacterial reverse mutation test performed according to OECD guideline 471 and GLP (CIT report No. 33249 MMO, 2007), Reaction Mass of Lanthanum Phosphate and Cerium Phosphate and Terbium Phosphate was applied on five strains of Salmonella typhimurium (TA1535, TA1537, TA98, TA100 and TA 102), using both plate incorporation and preincubation methods, at concentrations between 156.3 to 5000 µg/plate, with or without metabolic activation in 2 independent experiments. The test substance did not induce any noteworthy increase in the number of revertants, both with and without S9 mix, in any of the six tester strains.

The potential of Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate to induce structural chromosomal aberrations was investigated in cultured human lymphocytes, according to OECD guideline 473 and GLP (CIT report No. 33250MLH, 2007).

Human lymphocytes were exposed to the test substance or positive-controls with and without metabolic activation system from liver fraction of Aroclor 1254-induced rats (S9 mix). The treatment-levels were as follows:

- in the 1stassay, the cells were exposed to 0.08 to 10 mM, with or without S9 mix, for 3 hours and then rinsed. Cells were harvested 20 hours after the beginning of treatment, corresponding to approximately 1.5 normal cell cycles;

- in the second assay without S9 mix, cells were exposed to 0.08 to 5 mM continuously until harvest. In the second assay with S9 mix, cells were exposed to 0.16 to 5 mM for 3 hours and then rinsed. Cells from the 2d experiment were harvested 20 hours and 44 hours after the beginning of treatment.

Experiments without S9 mix:

A slight to marked toxicity was induced at dose-levels ≥0.63 mM following the 3-hour treatment. Following the 20-hour and 44-hour treatments, no decrease in mitotic index was observed except for a slight decrease in mitotic index noted at 5mM. However, the evaluation of mitotic index may have been altered due to the presence of strong precipitate on the slides.

Metaphase analysis:

No significant increase in the frequency of cells with structural chromosomal aberration was noted after 3-, 20- as well as 44-hour treatments.

Experiments with S9 mix:

A slight to strong toxicity was observed at dose-levels ≥1.25mM.

Metaphase analysis:

No significant increase in the frequency of cells with structural chromosomal aberration was noted in either experiment and at either harvest time.

The frequencies of cells with structural chromosome aberration of the vehicle and positive controls were as specified in acceptance criteria. The study was therefore considered valid.

Under our experimental conditions, the test item reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate did not induce chromosome aberrations in cultured human lymphocytes.

The potential of Reaction mass of lanthanum phosphate and cerium phosphate and terbium phosphate to cause gene mutation was investigated in CHO K1 Chinese hamster ovary cells at the hprt locus, according to OECD guideline 476, and Commission Regulation (EC) No.440/2008, B.17, and in compliance with OECD Principles of Good Laboratory Practice (CiToxLAB report n°12/262-015C, 2013).

Treatments were carried out for 5 hours with and without metabolic activation (±S9-mix) and for 24 hours without metabolic activation (-S9-mix). Distilled water was used as solvent.

Treatment concentrations for the mutation assay were selected for the main tests based on the results of a preliminary toxicity test as follows:

Assay 1:

- 5-hour treatment in the presence or absence of S9-mix: 2500; 1250; 625; 312.5; 156.25; 78.13; 39.06 and 19.53 µg/mL

Assay 2:

- 5-hour treatment in the presence of S9-mix: 2500; 1250; 625; 312.5; 156.25; 78.13; 39.06 and 19.53 µg/mL

- 24-hour treatment in the absence of S9-mix: 1500; 1250; 1000; 750; 500; 250; 125; 62.5; 31.25 and 15.63 µg/mL

No biologically significant increases in the numerical value of the mutation frequency compared to the vehicle control were observed at any examined concentrations and there was no dose response to the treatment.

There were no large changes in the pH or osmolality.

In Assay 1 and 2, in the presence of S9-mix (5-hr treatment), no cytotoxic effect of the test item was observed. In the absence of S9-mix, cytotoxicity was observed at 2500 µg/mL (Assay 1, 5-hr treatment) and at 750 µg/mL and higher (Assay 2, 24-hr treatment).

Precipitation was observed in the treatment medium at the end of the treatment at 125 µg/mL or higher in both assays in the presence or absence of metabolic activation.

The positive controls induce the appropriate response and the overall study was considered to be valid.

No mutagenic effect of Reaction mass of Lanthanum Phosphate and Cerium Phosphate and Terbium Phosphate was observed either in the presence or absence of metabolic activation system under the conditions of this HPRT assay.

 

Reaction Mass of Lanthanum Phosphate and Cerium Phosphate and Terbium Phosphate did not induce any mutation or chromosome aberration in 3 different in vitro studies and therefore should not be classified for genetic toxicity.

 

Genetic toxicity in vivo

No data is available on the genetic toxicity in vivo endpoint. As Reaction Mass of Lanthanum Phosphate and Cerium Phosphate and Terbium Phosphate was tested negative in vitro tests (Ames test, mammalian chromosome aberration test and mammalian gene mutation assay), therefore no in vivo genetic toxicity assay should be performed in accordance with column 2 adaptation of REACH regulation Annex VIII, section 8.4. 


Justification for selection of genetic toxicity endpoint
Endpoint selection:
- Gen. tox in vitro V1 2007 CIT (report 33249 MMO)
- Gen. tox in vitro V1 2007CIT (report 33250 MLH)
- Gen. tox in vitro 2013 CitoxLAB (report 12/262-015C)
Key studies quoted as reliability 1 according to Klimisch criteria (performed according to OECD guidelines and in accordance with GLP)

Short description of key information:
No indication of genetic toxicity based on in vitro test results : Ames test, mammalian chromosome aberration test and mammalian gene mutation test.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the classification criteria of Annex VI Directive 67/548/CEE or UN/EU GHS, and considering the negative results in the three in vitro genetic toxicity tests using Reaction Mass of Lanthanum Phosphate and Cerium Phosphate and Terbium Phosphate, no classification for mutagenicity is required.

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