Mutagenicity testing of diethylene glycol monobutyl ether.

The mutagenic potential of diethylene glycol monobutyl ether (diEGBE) was examined with a Tier I battery of in vitro assays followed by a Tier II in vivo Drosophila sex-linked recessive lethal assay. The in vitro battery consisted of: the Salmonella mutagenicity test, the L5178Y mouse lymphoma test, a cytogenetics assay using Chinese hamster ovary cells and the unscheduled DNA synthesis (UDS) assay in rat hepatocytes. Results of the Salmonella mutagenicity test, the cytogenetics test, and the rat hepatocyte assay were negative at concentrations up to 20 microL/plate, 7.92 microL/mL, and 4.4 microL/mL, respectively. Toxicity was clearly demonstrated at all high doses. A weak, but dose-related increase in the mutation frequency (4-fold increase over the solvent control at 5.6 microL/mL with 12% survival) was obtained in the L5178Y lymphoma test in the absence of metabolic activation. Results of the mouse lymphoma assay were negative in the presence of the S-9 activation system. The significance of the mouse lymphoma assay were negative in the presence of the S-9 activation system. The significance of the mouse lymphoma assay results were assessed by performing the Tier II sex-linked recessive lethal assay in Drosophila in which the target tissue is maturing germinal cells. Both feeding (11,000 ppm for 3 days) and injection (0.3 microL of approximately 14,000 ppm solution) routes of administration were employed in the Drosophila assay. Approximately 11,000 individual crosses with an equal number of negative controls were performed for each route of administration. diEGBE produced no increase in recessive lethals under these conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Locus specificity of mutagenicity of 2,4-diaminotoluene in both L5178Y mouse lymphoma and AT3-2 Chinese hamster ovary cells.

2,4-Diaminotoluene, a hepatocarcinogenic aromatic amine, was tested for mutagenic potential at both the autosomal tk locus and the sex-linked hgprt locus of both L5178Y 3.7.2C mouse lymphoma cells and Chinese hamster ovary (CHO) AT3-2 cells. This compound was mutagenic in both cell types at the tk locus but not at the hgprt locus. Mutagenic activity was observed in L5178Y cells only in the absence of exogenous metabolic activation, but was observed in CHO-AT3-2 cells both with and without activation.

Unscheduled DNA synthesis and DNA repair studies of peroxyacetic and monoperoxydecanoic acids.

Peroxyacetic (PAA) and monoperoxydecanoic (MPDA) acids were assayed for induction of unscheduled DNA synthesis (UDS) by liquid scintillation counting of hot-acid-extractable DNA and by light microscope autoradiography. Both compounds were also assayed for induction of DNA repair synthesis by differential density labeling ultracentrifugation. Uniformly negative results were obtained for MPDA. Conflicting results were obtained for PAA using the UDS techniques. Negative results were consistently obtained, however, in three separate assays using two different PAA samples with the more definitive differential density DNA repair synthesis technique. Hydrogen peroxide, which is present as a contaminant in the PAA samples, was also assayed for induction of UDS by autoradiography and for induction of DNA repair synthesis by differential density labeling. Our results with this compound are in agreement with published data and were consistently positive using both techniques. We conclude that neither MPDA nor PAA induce DNA repair synthesis and suggest that the conflicting PAA results may be due to the presence of hydrogen peroxide in commercial samples of PAA.

Mutagenicity of alkyl glycidyl ethers in three short-term assays.

The mutagenic potential of glycidol and 7 alkyl glycidyl ethers having straight alkyl chains of 2, 4, 6, 8, 10, 12, and 14 carbon atoms were examined in a battery of in vitro assays. The battery consisted of the Salmonella/mammalian microsome assay, the L5178Y mouse lymphoma assay, and unscheduled DNA synthesis using W138 cells. The mutagenic potential of the compounds ranged from strongly mutagenic to non-mutagenic; glycidol exhibited the greatest activity. All the ethers through C-4 showed a definite response whole the C-8 or higher ethers showed very weak or no responses. Dose-response curves were obtained by all 3 assays for those compounds that exhibited mutagenic activity. The sensitivity of each assay is discussed, as are the effects of the liver microsome systems used for metabolic activation.