Lethality testing

Tripathy NK, Dey L, Majhi B, et al. 1987. Genotoxicity of metacid established through the somatic and germ line mosaic assays and the sex-linked recessive lethal test in drosophila. Arch Toxicol 61 53-57. 

Insect systems Drosophila melanogaster (sex-linked recessive lethal test) Recessive lethal mutation + Velazquez et al. 1984... 

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

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. 

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 selecting dosages for an acute systemic toxicity study, the same general guidelines apply as with lethality testing ... 

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. 

Environmental Protection Series (EPS). Biological Test Method Acute Lethality Test Using Daphnia spp. Report EPS 1/RM/ll, Environment Canada, 1990 57 pp. 

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

Sex-linked recessive lethal test in Drosophila melanogaster (August 1998)... 

B.20 Sex-Linked Recessive Lethal Test in Drosophila melanogaster (1988)... 

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... 

A positive response in the rodent dominant lethal test indicates that the test substance may be genotoxic in the germ cells of the treated sex of the test species as evaluated by an increase in the number of dominant lethals evaluated as the sum of pre- and postimplantation loss. A dominant lethal mutation is one occurring in a germ cell, which does not cause dysfunction of the gamete but which is lethal to the fertilized egg or developing embryo. 

Gollapudi BB, Cieszlak FS, Day SJ, et al Dominant lethal test with rats exposed to 1,3 -dichloropropene by inhalation. Environ Mol Mutagen 32(4) 351-9, 1998... 

Methyl chloride was mutagenic to bacteria and genotoxic in a number of mammalian cell systems in vitro. " It gave positive results in the dominant lethal test in rats in vivo ... 

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." ... 

Studies evaluating the genotoxic potential of hexachlorobutadiene indicate that hexachlorobutadiene does not affect fertility in male rats. In dominant lethal tests in rats, fertility indices, number of corpora lutea or implantations, or the frequency of early death did not differ between animals that inhaled vapors of hexachlorobutadiene at concentrations up to 50 ppm and their unexposed controls (NIOSH 1981). 

Hazleton Labs. 1989d. Mutagenicity test on ortho-cresol (lot number RC645A) Drosophila Melanogaster sex-linked recessive lethal test. HLA study no. 10004-0-461. Unpublished data submitted to Chemical Manufacturers Association, Washington, DC. 

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