Responses of the L5178Y mouse lymphoma forward mutation assay: V. Gases and vapors

Abstract

A new protocol for testing vapors and gases in the L5178Y mouse lymphoma assay is presented. Four chemicals, propylene, 1,2-propylene oxide, 1,3-butadiene, and vinylidene chloride, were tested for their mutagenic potential. Cultures were exposed to the chemicals, which were delivered as vapors or gases, for 4 hr, then cultured for 2 days before plating in soft agar with or without trifluorothymidine (TFT), 3 microgram/ml. Each chemical was tested at least twice. Significant responses were obtained with 1,2-propylene oxide and vinylidene chloride, but neither cytotoxicity nor mutagenicity was induced by 1,3-butadiene; propylene could not be classified as either mutagenic or non-mutagenic in the assay. Rat liver S9 mix was not a requirement for the mutagenic activity of 1,2-propylene oxide, whereas the liver preparation markedly enhanced both the cytotoxicity and mutagenicity of vinylidene chloride.

Assessment of 1,3-Butadiene Exposure in Polymer Production Workers Using HPRT Mutations in Lymphocytes as a Biomarker

“…BD was mutagenic in Salmonella typhimurium strain TA 1530 with metabolic activation (7), and BD gas was weakly mutagenic in the mouse lymphoma assay in the presence of rat liver S9 (8). In laboratory animals, BD can induce chromosomal damage and somatic cell mutations.…”

Renal Cell Carcinomas in Vinylidene Chloride–exposed Male B6C3F1 Mice Are Characterized by Oxidative Stress and TP53 Pathway Dysregulation

“…Various studies indicate that VDC, with metabolic activation, is genotoxic in bacteria, yeast, and fungi (Bartsch et al 2000; Bronzetti et al 1981; Henschler and Bonse 1977). However, genotoxicity studies in mammalian cells have been equivocal (Drevon and Kuroki 1979; McGregor et al 1991), and unlike Vinyl chloride (Whysner et al 1996), DNA adduct formation has not been reported (Whysner et al 1996). Similarly, results were equivocal in the current NTP genotoxicity testing (NTP TR582) (National Toxicology Program 2015).…”

Aliphatic Hydrocarbons

“…It is not cytotoxic or mutagenic in cultures of mouse lymphoma cells in either presence or absence of a hepatic microsomal activating system (382). In mouse peripheral tissues and hemoglobin, propene is six times less potent an alkylating agent than propene oxide (377).…”