Mutagenic activity of 3 industrial chemicals in a battery of in vitro and in vivo tests.

3 chemicals were selected for mutagenicity testing from a priority list, based on production volume and available mutagenicity data. Propargyl alcohol (PA), 2-nitroaniline (2NA), and 5-methyl-1H-benzo-triazole (MBT) were selected for testing using the approach recommended in the Health Protection Branch Genotoxicity Guidelines. The battery of tests included the Salmonella/mammalian microsome mutation assay, the in vitro chromosomal aberration assay, and the bone-marrow micronucleus assay. The results indicate that 2 of the 3 chemicals, PA and 2NA, were clastogenic in vitro. Both PA and 2NA induced chromosomal aberrations in CHO cells in vitro with and without metabolic activation, while none induced reverse mutations detectable with the Salmonella/mammalian microsome assay. Because PA and 2NA were found to be in vitro clastogens, they also were tested in the mouse bone-marrow micronucleus assay. 2NA induced a small increase in micronuclei in males but not females. PA did not induce an increase in micronuclei.

Mutagenic activity of p-toluenesulfonhydrazide.

Toluenesulfonhydrazide (TSH) is a high volume production chemical for which there is relatively little toxicological data. In this study, the mutagenic activity of TSH was determined in the Salmonella/mammalian microsome assay and the in vitro chromosomal aberration assay using Chinese hamster ovary cells. TSH induced gene mutations both with and without metabolic activation in the Salmonella/mammalian microsome assay but that it did not induce chromosomal aberrations in Chinese hamster ovary cells. The results of this study indicate that TSH is an in vitro mutagen and should be assessed for in vivo mutagenicity.

The SIMULTEST: a new approach to screening chemicals with the Salmonella reversion assay.

A new Salmonella mutagenicity test method is under development to test a chemical with more than one strain simultaneously (the "SIMULTEST"), that is, different Salmonella typhimurium tester strains are used in combination on the same plate. Strains are combined in two sets: strains with plasmid pKM101 (TA97, TA98, TA100, and TA102) and strains without the plasmid (TA1535, TA1537, and TA1538). The SIMULTEST combinations successfully detect the mutagenic activity of five mutagens in different chemical classes. This approach may be useful in reducing the workload associated with mutagenicity testing with Salmonella.

Mutagenicity studies on herring gulls from different locations on the Great Lakes. II. Mutagenic evaluation of extracts of herring-gull eggs in a battery of in vitro mammalian and microbial tests.

Herring-gull (Larus argentatus) eggs were collected from five locations on the Great Lakes and from one colony on the Atlantic coast for organochlorine analysis and mutagenesis testing. The Great Lakes colonies were chosen for their different contaminant levels, while the Atlantic coast colony was used as a relatively clean control. The eggs were homogenized and extracted, and the extracts were tested in the Salmonella/mammalian microsome assay for induction of point mutations and in Chinese hamster ovary (CHO) cells for the induction of sister chromatid exchanges (SCEs) and chromosome aberrations. None of the extracts was mutagenic in Salmonella, either in the presence or absence of metabolic activation. However, all of the extracts, including the clean control, caused significant increases in both the SCE rate and in the number of chromosome aberrations in the CHO cells. There was no apparent relationship between contaminant levels and the magnitude of these responses or the doses at which they occurred, although the chemical analysis indicated a wide range in the concentrations of the different organochlorides present.