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Key value for chemical safety assessment

Additional information

Genotoxicity in vitro:

The genotoxic potential of TBEP has been investigated in two test systems in vitro. Gene mutation studies have been carried out using bacteria and mammalian cells. Chromosomal aberration has not been investigated in mammalian cells in vitro, but this endpoint is covered by anin vivostudy.

In a reverse gene mutation assay in bacteria (Haworth, 1979), strains TA1535, TA1537, TA1538, TA98 and TA100 of S. typhimurium were exposed to TBEP, in DMSO, at concentration of 0.02, 0.1, 0.5, 1.4 & 2.8 microlitres per plate in the presence and absence of mammalian metabolic activation. The positive controls induced the appropriate responses in the corresponding strains. There was no evidence of induced mutant colonies over background. This key study satisfies the requirement of Test Guideline OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation).

The potential of TBEP for mutagenicity in mammalian cells has been investigated using the Chinese Hamster Ovary HGPRT mammalian cell forward gene mutation assay with and without metabolic activation (Kirby, 1981). Test concentrations were 50, 100, 150, 225 and 300 micrograms per ml with 5% S9; 5, 50, 75, 100 and 130 micrograms per ml in the absence of S9. Cytotoxicity was observed at the highest dose level with a dose-related trend both in presence and absence of S9. There was no evidence of mutagenicity at any dose tested, with or without metabolic activation.

The full study report was not available for assessment, however the data have been peer-reviewed in two reference works (IPCS EHC 218, 2000 and ECETOC JACC report 21, 1992). The data reported in these publications is considered adequate to satisfy the requirements for this endpoint.

Genotoxicity in vivo:

The potential of TBEP for genotoxicityin vivohas been investigated in the micronucleus test (OECD 474). TBEP was administered to male and female mice once by gavage at doses of 0 and 1800 mg/kg. The animals were killed 24, 48 or 72 hours after the administration of the test compound. The number of polychromatic and normochromatic erythrocytes containing micronuclei was not increased. The ratio of polychromatic/normochromatic erythrocytes was not affected by treatment in male or female mice. TBEP was considered not mutagenic in the micronucleus test.


Short description of key information:
The genotoxic potential of TBEP has been investigated both in vitro and in vivo. All tests gave negative results, leading to the conclusion that TBEP is not genotoxic. For in vitro gene mutation studies in bacteria, a study similar to OECD guideline 471, Haworth (1979), (Rel 2) has been chosen as the key study. For in vitro mammalian cell gene mutation, an HGPRT mammalian cell forward gene mutation assay in CHO cells (Kirby, 1981) performed according to OECD guideline 476 (Rel 2) has been chosen as key study. No in vitro chromosomal aberration study in mammalian cells is available, however this endpoint is covered by an in vivo mouse micronucleus study in bone marrow cells.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

All in vitro and in vivo studies on TBEP gave a negative (non-genotoxic) result.

TBEP is therefore not classified for genotoxicity according to the criteria of Annex VI Directive 67/748/EECor EU/UN GHS.