Dominant Lethal Studies with the Halogenated Olefins Vinyl Chloride and Vinylidene Dichloride in Male CD-1 Mice

Abstract

JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org.. The National Institute of Environmental Health Sciences (NIEHS) and Brogan & Partners are collaborating with JSTOR to digitize, preserve and extend access to Environmental Health Perspectives. The mutagenic activity of vinyl chloride (VC) and vinylidene dichloride (VDC) at three exposure levels was assessed in ferti}e male CD-1 mice with the dominant lethal test. Each compound was assessed in a separate study.Male mice were exposed by inhalation to YC at 3000 10,000, and 30s00Q ppm and to VDC at 10, 30, and 50 ppm for 6 hr/day for 5 days. By comparison with control males exposed to air, no mutagenic effects on any maturation stage of spermatogenesis in treated males were detected. There was no significant inerease in the number of postimplantational early fetal deaths as shown by the number of females with one or more early deaths or the number of early deathslpregnancy or the number of early deaths/total implants/pregnancy. There was no evidence of pre-implantational egg losses as indicated by the total implants/pregnant female. There was also no reduction in fertility. (The reduction in fertility at 50 ppm VDC was unproven).The lack of effect was not due to the insensitivity of the system used, since both the VC and VDC study a mutagenic effect was clearly demonstrated in male mice dosed IP with the positive control compounds cyclophosphamide (CTX) and/or ethylmethane sultonate (EMS). During dosing these animals were housed under similar exposure conditions to those animals exposed to the test substances but with a flow of air through the exposure chambers.Thus neither VC nor VDC is mutagenic in the mouse at the stated exposure levels as measured by the dominant lethal test. this type in mice after VC and VDC exposure at three levels. At the same time negative control animals exposed to air and positive control animals also exposed to air and given EMS andXor CTX were assayed.

Mutagenicity studies of vinyl chloride.

“…In one of these studies, increased metabolites were observed in Chinese hamster V79 cells (15). However, in a study by Anderson et al (16), an increase in murine embryonic mortality was not seen in females mated to male mice who had received vinyl chloride prior to mating. These authors did report decreased fertility in the males which had received the highest dosage of vinyl chloride, or 50 ppm for 6 hr/day for 5 days.…”

“…These include one study using two different strains of Neurospora (12) a lambda prophage induction test (9), and dominant lethal tests in both mice (16) and rats (17). In addition, a cytogenetic study in man was also found to be negative in which both sister chromatid exchange frequencies, as well as chromosomal breakage, were studied following one five minute acute exposure to vinyl chloride (22).…”