Tests dominant lethal

Based on evidence derived from a large array of assays such as bacterial reverse mutation test, mammalian bone marrow chromosome aberration test, dominant lethal assay, and UDS assay, atrazine was concluded to lack mutagenic potential. 

Oral LD50 8100 mg/kg [Mouse], Intraperitoneal LD50 2190 mg/kg [Mouse]. Chronic Exposure - Teratogen Dose 837 mg/kg [Rat], Intraperitoneal exposure time (5-15D PREG) resulted in developmental abnormalities and fetal death. Chronic Exposure - Mutagen Dose 1100 mg/kg [Mouse], Intraperitoneal Dose llOOmg/Kg Mutation test Dominant lethal test. 

Dominant Lethal Test. Dominant lethal mutation is a genetic event that kills the individual which carries it. The damage, which notably consists of chromosomal-type mutations, is detected as preimplantation loss of non-viable blastocysts and as early embryonic death.14 Fetal wastage above the spontaneous background rate is attributed to dominant lethal mutations since only the males are treated with the test compound females can be treated also, although this test is more difficult to interpret. This test has been well evaluated by several investigators.15-21... 

Not mutagenic (Ames test, micronucleus test, dominant lethal test negative). 

Moderately irritant to skin and mucosa, contact dermatitis possible potential skin sensitizer. Not mutagenic (Ames test, micronucleus test, dominant lethal test negative). 

Not known to be a reproductive or development toxin or to be carcinogenic. - Mutagenicity test (dominant lethal assay) negative. 

Ethylene oxide has been shown to produce mutagenic and cytogenic effects in a variety of test systems (226). An increased frequency of chromosomal aberrations in peripheral lymphocytes of monkey exposed to ethylene oxide for 104 weeks has been reported (240). In mice, it is an effective inducer of chromosome breaks leading to dominant-lethal mutations. In addition, ethylene oxide has been shown to induce heritable effects in the heritable translocation test conducted in mice exposed to ethylene oxide by inhalation (241,242). In this study, male mice were exposed to ethylene oxide ranging from 165 to 300 ppm for 6 h per day 5 or 7 days/week for 8.5 weeks. Ethylene oxide has also been shown to bind to proteins (243) as well as to DNA (244). Several studies on ethylene oxide-exposed workers have demonstrated an increased incidence of chromosomal aberrations and sister chromatid exchanges the relevance of such effects to human health evaluation is currendy uncertain. 

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... 

Polychlorodibenzo- -dioxins Perinatal Effects and the Dominant Lethal Test in Wistar Rats... 

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. 

Reproductive Effects. Reproductive effects have not been examined in humans after exposure to -hexane. A dominant-lethal test in mice showed no effect on male fertility (Litton Bionetics 1980). No effects were seen on reproductive tissues in male rats after intermediate-duration inhalation exposure at 500 ppm (IRDC 1981) or in either sex of mice after intermediate-duration inhalation exposure to up to 10,000 ppm -hexane (Dunnick et al. 1989 NTP 1991). However, inhalation exposure in male rats to higher concentrations of -hexane showed effects after acute-duration exposure to 5,000 ppm (spermatid and spermatocyte degeneration and exfoliation) and atrophy of testicular germinal epithelium after intermediate-duration exposure to 1,000 ppm (De Martino et al. 1987 Nylen et al. 1989). Testicular atrophy in rats was also noted after intermediate-duration oral exposure at 4,000 mg/kg/day (Krasavage et al. 1980). Similar to -hexane neurotoxicity after inhalation exposure, effects on the testes in rats can be reproduced by oral administration of the w-hexane metabolite 2,5-hexanedione (Chapin et al. 1982 ... 

In a dominant lethal test, treatment of male mice with a single oral dose of 5 mg/kg disulfoton had no effect on male fertility (Herbold 1980). In a three-generation reproductive study, exposure of male and female rats to disulfoton in the diet at 0.5 mg/kg/day resulted a "slight" reduction of litter sizes in... 

Disulfoton was negative in a dominant lethal test in male mice treated orally with a single dose ot S mg/kg (Herbold 1980) and in an erythrocyte micronucleus test in mice dosed with 6 or 12 mg/k /day for 2 days (Herbold 1981). Disulfoton also did not induce micronuclei in erythrocytes of mice dosed with 2, 4, or 8 mg/kg disulfoton (EPA 1984a Sandhu et al. ]985), but whether disulfoton was administered by the oral or intraperitoneal route was not clear. Other genotoxicity studies are discussed in Section 2.4. 

Flerbold B. 1980. Dominant lethal test on male mouse to evaluate S276 for mutagenic potential. Report No. 9440. Bayer AG, Institute of Toxicology, Wuppertal-Elberfeld, Germany. 

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. 

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). 

There are very few in vivo genotoxicity studies. Only two in vivo studies were located, and both assessed the dominant lethal effects. The results were negative for both studies, implying that neither heptachlor nor heptachlor epoxide are genotoxic to the germ-line cells of male mice when tested alone or as a mixture (Arnold et al. 1977 Epstein et al. 1972). Refer to Table 2- 3 for a summary of these results of in vivo studies. 

Genetic Toxicology Rodent Dominant Lethal Test (Updated Guideline, adopted 4 April 1984)... 

Genetic toxicology Rodent dominant lethal test... 

B.ll Mutagenicity - In vivo mammalian bone-marrow chromosome aberration test B.12 Mutagenicity mammalian erythrocyte micronucleus test B.20 Sex-Unked recessive lethal test in Drosophila melanogaster B.22 Rodent dominant lethal test... 

The rodent dominant lethal test OECD TG 478 US-EPA OPPTS 870.5450 EU Annex V B.22... 

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