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Key value for chemical safety assessment

Additional information

The genotoxic potential of TEPA has been investigated in three test systems in vitro.

Gene mutation studies have been carried out using bacteria and mammalian cells. Chromosomal aberration has been investigated in mammalian cells.

The mutagenic potential of TEPA in bacteria was evaluated in the Ames test using four strains of Salmonella typhimurium (TA1535, TA1537, TA98, TA100) and one strain of Escherichia coli (WP2 uvrA), following protocols complying with OECD Guidelines Numbers 471 and 472. In two separate experiments in triplicate, TEPA did not induce any significant, reproducible increases in the observed numbers of revertant colonies in any test strain either in the presence or absence of S9 mix up to 5000 µg/plate. In each experiment, the positive controls responded as expected indicating that the assay was performing satisfactorily. Under the conditions of this assay, TEPA therefore gave a negative, i.e. non-mutagenic, response in bacteria.

The potential of TEPA for mutagenicity in mammalian cells was investigated using the mouse lymphoma test in the cell line L5178Y. The assay was performed in two independent experiments, using two parallel cultures. The first experiment was performed with and without liver microsomal activation and a treatment period of 4 h. The second experiment was performed with a treatment time of 24 hours in the absence of metabolic activation. No substantial and reproducible dose dependent increase of the mutation frequency was observed in either experiment up to the maximum concentration (2250 µg/mL, i.e. approx 10 mM) with and without metabolic activation. The positive controls showed a distinct increase in induced total mutant colonies and an increase of the relative quantity of small versus large induced colonies. Under the conditions of this test, TEPA was not mutagenic in the mouse lymphoma thymidine kinase locus assay using the cell line L5178Y.

TEPA was assessed for its potential to induce structural chromosome aberrations in Chinese hamster V79 cells in three experiments in duplicate with and without metabolic activation in accordance with OECD Guideline 473. No reproducible clastogenicity was observed either with or without metabolic activation up to the highest required concentration (2250 µg/mL, i.e. approx.10 mM). No relevant increase in the frequencies of polyploid metaphases was found after treatment with the test item as compared to the frequencies of the controls. Appropriate positive controls induced statistically significant increases in cells with structural chromosome aberrations. Under the experimental conditions reported, TEPA did not induce structural chromosome aberrations as determined by the chromosome aberration test in Chinese hamster V79 cells. TEPA is therefore considered to be non-clastogenic in this test.

According to the column 2 of Annex VIII, in vivo mutagenicity studies shall be considered in case of a positive result in any of the genotoxicity studies in Annex VII or VIII. In the present case, as all the in vitro studies performed on the submitted substance showed negative results, there is no datagap: no in vivo study is required.


Justification for selection of genetic toxicity endpoint
No study was selected since all three in vitro studies are negative

Short description of key information:
The genotoxic potential of TEPA has been investigated in vitro.
Ames test (OECD 471, GLP, 2000, Kr. 1): negative +/- S9 mix in S. typhimurium and E. coli
Chromosome aberrations (OECD 473, GLP, 2007, Kr. 1) : negative +/- S9 mix in Hamster V79 cells
Mouse Lymphoma assay (OECD 476, GLP, 2006, Kr. 1): negative +/- S9 mix in L5178Y cells

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Self-classification:

Based on the available in vitro data, Triethyl phosphonacetate did not show any evidence of mutagenicity or clastogenicity, and therefore is not classified for genotoxicity according to the Regulation (EC) 1272/2008 (CLP) and the directive 67/548/EEC.