Dominant-lethal assay

Mouse visible or eleetrophoretie specifie-locus tests Assays for skeletal and cataract mutations Cytogenetic analy.sis and heritable translocation assays DNA damage and repair in rodent germ cells Dominant lethal assay... 

Dominant Lethal Assay. All doses of 8-D used in the dominant lethal study were toxic for the male rats. The highest dose, 12 /xg/kg/day, was lethal for 20/20 males (mean survival, 17.7 days), 8 jug/kg/day killed 11/20 males (mean survival, 20.1 days), and 4 /xg/kg/day was lethal for 2/20 (mean survival, 36.5 days). There were no mortalities in the control group. 

Monomethylhydrazine-induced mutagenesis was not observed in Ames Salmonella/ microsome with activation (Matheson et al. 1978). In vivo tests in mice (dominant lethal, revertants in host-mediated assay), and dogs (micronuclei) were negative (reviewed in Trochimowicz 1994). However, in vitro chromosomal damage in human and rat tissue has been demonstrated, although in vivo liver DNA damage (as determined by DNA alkaline elution) was equivocal (reviewed in Trochimowicz 1994). 

Brusick and Matheson (1976) reported that 1,1-dimethylhydrazine failed to increase reversions in Salmonella typhimurium or Saccharomyces cerevisiae gene mutation assays with or without metabolic activation. A concentration-related response was observed in the mouse lymphoma assay (with activation). Dominant lethal tests were negative. 

Matheson et al. (1978) reported the results of a battery of in vivo and in vitro assays to assess the genotoxicity of 1,1-dimethylhydrazine. Included were the Ames Salmonella microsome assay, a microbial suspension assay, mutation induction at the TK locus in L5178Y mouse lymphoma cells, stimulation of UDS in WI-38 cells, and a dominant lethal assay in mice. 1,1-Dimethylhydrazine was active in all of the tests except the dominant lethal assay. 

Shukla Y, Taneja P (2002) Mutagenic potential of cypermethrin in mouse dominant lethal assay. J Environ Pathol Toxicol Oncol 21 259-265... 

In a dominant lethal assay in male CD-I mice, /i-hcxanc exposure at 99 or 396 ppm for 6 hours a day,... 

Litton Bionetics. 1980. Mutagenicity evaluation of M-hexane in the mouse dominant lethal assay Final report. Unpublished study by Litton Bionetics Inc., Kensington MD. Prepared for the American Petroleum Institute, Washington DC. EPA-FYI-AX-0183-0231. 

Simon GS, Egle JL, Dougherty RW, et al. 1986. Dominant lethal assay of chlordecone and its distribution in the male reproductive tissues of the rat. Toxicol Lett 30 237-245. 

Buselmaier W, Roehrborn G, Propping P. 1972. [Mutagenicity investigations with pesticides in host-mediated assay and dominant lethal test in mice], Biol ZbI 91 311-325. 

Epstein SS, Arnold E, Andrea J, et al. 1972. Detection of chemical mutagens by the dominant lethal assay in the mouse. Toxicol AppI Pharmacol 23 288-325. 

In a dominant lethal assay, eight male Charles River CD-I mice received single oral doses of 7.5 or 15 mg/kg of a heptachlor heptachlor epoxide mixture (25% 75%) and were bred with three untreated females each week for 6 weeks (Arnold et al. 1977). No adverse effect on the reproductive capacity of male mice was noted therefore, the NOAEL was 15 mg/kg. A LOAEL was not established. Both heptachlor and heptachlor epoxide were also tested separately in another dominant lethal assay in mice. Heptachlor was tested at 5 and 10 mg/kg and heptachlor epoxide at 8 mg/kg/day. Neither agent produced early fetal deaths or preimplantation losses outside the control limits (Epstein et al. 1972). 

Mammalian cells CD-I mouse (dominant lethal assay) Swiss mouse (dominant lethal assay) Domi nant Domi nant 1ethal 1ethal. a, b a, c Arnold et al. 1977 Epstein et al. 1972... 

API. 1981. Mutagenicity evaluation of diesel fuel in the mouse dominant lethal assay. Washington, DC American Petroleum Institute. 

In two three-generation studies with rats administered heptachlor, heptachlor epoxide, or a mixture of the two in the diet, the number of resorbed fetuses increased and the fertility decreased with succeeding generations. No adverse effects on reproductive capacity were reported in male mice receiving single oral doses of 7.5 or 15mg/kg heptachlor heptachlor epoxide (25% 75%) in a dominant lethal assay. Heptachlor epoxide has been found in tissues of stillborn infants, indicating transplacental transfer. ... 

Negative results were reported in various mutagenic assays including the Ames Salmonella assay (with or without microsomal activation), sister chromatid exchange assay in mouse lymphoma cells, mouse bone marrow cyto-genic analysis, and mouse dominant lethal assay ... 

Stodddard solvent was not genotoxic in a variety of assays including Salmonella typhimurium, a mouse lymphoma mutation assay, rodent bone marrow cytogenic tests, and rodent dominant lethal tests." ... 

Toxaphene has been found to be genotoxic in a number of assays. It was mutagenic in Sal-Ttimella typhimurium, and increased the frequency of sister chromatid exchanges in cell culture. In one study toxaphene-exposed individuals had a higher incidence of chromosomal aberrations in lymphocytes than controls. However, in vivo toxaphene did not bind to DNA or produce dominant lethal mutations. ... 

T was not mutagenic in bacterial assays, and it did not induce aneuploidy or somatic mutation in vitro. In vivo it did not cause micronuclei in mice or dominant lethal mutations in mice or rats. ... 

Dominant lethal assays in mice were performed using o- and p-cresols. Male mice were given a single dose of o-cresol (0, 75, 250, or 750 mg/kg) or p- cresol (0, 100, 275, or 550 mg/kg) by gavage in corn oil and mated to untreated females in order to assess dominant lethal effects. The matings were continued for 6 weeks so that all stages of male germ cell development were tested. 

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