Neodymium trifluoride

Endpoint summary

Additional information

In vitro gene mutation in bacteria

The potential of the test material to cause mutagenic effects in bacteria was assessed in accordance with the standardised guidelines OECD 471 and EU Method B.13/14. Furthermore, the test method was designed to be compatible with the guidelines for bacterial mutagenicity testing published by the major Japanese Regulatory Authorities including METI, MHLW and MAFF and the USA, EPA (TSCA) OPPTS harmonised guidelines.

Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and Escherichia coli strain WP2uvrA were treated with the test material, using the plate incorporation and pre-incubation methods, at five dose levels, both with and without metabolic activation. The dose levels assessed were 50, 150, 500, 1500 and 5000 µg/plate.

The test material caused no visible reduction in the growth of the bacterial background lawn at any dose level. The test material was, therefore, tested up to the maximum recommended dose level of 5000 μg/plate.

No toxicologically significant increases in the frequency of revertant colonies were recorded for any of the bacterial strains. 

The vehicle controls gave revertant colony counts within the normal range. The positive controls gave the expected increases in revertants, validating the sensitivity of the assay and the efficacy of the S9-mix.

The test material was considered to be non-mutagenic under the conditions of this test.

 

In vitro gene mutation in mammalian cells

A study was conducted to assess the potential mutagenicity of the test material on the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus of Chinese hamster ovary (CHO) cells in vitro in accordance with the standardised guidelines OECD 476, EU Method B.17, the United Kingdom Environmental Mutagen Society (Cole et al, 1990) and the EPA OPPTS 870.5300.

CHO cells were treated with the test material at six dose levels, in duplicate, together with negative and positive controls. The technique used is a plate assay using tissue culture flasks and 6-thioguanine (6-TG) as the selective agent.

Two treatment conditions were used for the test. In Experiment 1, a 4 hour exposure in the presence of 2 % S9 and in the absence of metabolic activation. In Experiment 2, the 4 hour exposure was repeated using a 1 % final S9 concentration, whilst in the absence of metabolic activation the 4 -hour exposure was repeated with to verify a possible response seen in Experiment 1.

The negative (Ham’s F12 culture medium) controls gave mutant frequencies within the range expected for CHO cells at the HPRT locus. The positive control treatments, both in the presence and absence of metabolic activation, gave significant increases in the mutant frequency indicating the satisfactory performance of the test and of the metabolising system.

 

The test material did not induce any significant or dose-related increases in mutant frequency per survivor at any dose level in the presence of metabolic activation in either of the two experiments.

Under the conditions of this study, the test material is considered to be non-mutagenic to CHO cells at the HPRT locus.

 

In vitro cytogenicityinmammalian cells

The potential of the test material to induce chromosomal aberrations was investigated in vitro in accordance with the standardised guidelines OECD 473, EU Method B.10 and the UK Department of Health Guidelines for Testing of Chemicals for Mutagenicity.

Duplicate cultures of human lymphocytes, treated with the test material, were evaluated for chromosome aberrations at three dose levels, together with negative and positive controls. The dose levels used in Experiment 1 in both the presence and absence of metabolic activation and Experiment 2 in the presence of metabolic activation were 0, 11.25, 22.5, 45, 90, 180 and 360 µg/mL. In Experiment 2 in the absence of metabolic activation, the dose levels selected were 0, 22.5, 45, 90, 180, 360 and 720 µg/mL.

Four treatment conditions were used for the study:

In Experiment 1, cells were exposed for 4 hours in the presence of an induced rat liver homogenate metabolising system (S9 at a 2 % final concentration) with cell harvest after a 20 hour expression period and a 4 hour exposure in the absence of metabolic activation with a 20 hour expression period.

In Experiment 2, the 4 hours exposure period with addition of S9 was repeated (using a 1 % final S9 concentration) whilst in the absence of metabolic activation the exposure time was increased to 24 hours.

All negative controls had frequencies of cells with aberrations within the range expected for normal human lymphocytes.

All the positive control materials induced statistically significant increases in the frequency of cells with aberrations indicating that the sensitivity of the assay and the efficacy of the S9-mix were validated.

The test material did not induce any statistically significant increases in the frequency of cells with aberrations in the exposure groups dosed in the presence or absence of S9 with dose levels based on the presence of precipitate.

Under the conditions of the study, the test material was considered not to induce any statistically significant increases in the frequency of cells with aberrations and, therefore was considered to be non-clastogenic.

Justification for selection of genetic toxicity endpoint
Three studies have been selected as key to address the genetic toxicity endpoint. No key study could be selected as all three studies address different genetic toxicity effects. All are well reported studies conducted in accordance with standardised testing guidelines and performed under GLP conditions and were therefore assigned reliability scores of 1 in accordance with Klimisch (1997).

Short description of key information:
In vitro gene mutation in bacteria (Ames): Harlan (2013): Negative with and without metabolic activation.
In vitro gene mutation in mammalian cells (CHO HPRT): Harlan (2013): Negative with and without metabolic activation.
In vitro cytogenicity in mammalian cells (Chrom Ab): Harlan (2013): Negative with and without metabolic activation.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the test material does not require classification for genetic toxicity.