Heritable translocation test

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. 

Damage may be analyzed in the heritable translocation test, which involves the examination in male F, animals if diakinesis metaphase 1 spermatocytes for multivalent association fall within the acceptable range for the laboratory for a substance to be considered positive or negative under the conditions of the study. 

A positive response in the mouse heritable translocation test indicates that exposure to the test substance results in an increase in the number of translocations observed for at least one test point, or an increase in the number of translocations observed, as a result of heritable gene mutations. 

Glycidol gave a positive response in assays of prophage induction and SOS repair m Escherichia coli. Results were uniformly positive in several Salmonella typhimurium reverse mutation assays and in two fungal mutation assays. The sex-linked recessive lethal mutation assay and the heritable translocation test in Drosophila melanogaster also gave positive results. 

MHT, Mouse heritable translocation test + 40 ip X 1 Lang Adler (1977)... 

Adler, I.-D. (1980) New approaches to mutagenicity studies in animals for carcinogenic and mutagenic agents. I. Modification of the heritable translocation test. Teratog. Carcinog. Mutag., 1, 75-86... 

Lang. R. Adler. I.-D. (1977) Heritable translocation test and dominant-lethal assay in male mice with methyl methanesulfonate. Mutat. Res., 48, 75-88... 

DMH, Drosophila melanogaster, heritable translocation test + 1800 ppm feed Kortselius (1979)... 

MHT, Mouse heritable translocation test in vivo - 100 po X 1, 8 wk Jorgenson Rushbrook... 

Mammals Cytogenetic damage Mouse Heritable-translocation test Semisterility, confirmed by cytogenetic detection of translocations <9 mo M VH M L... 

As shown in Figure 9-1, a clearly positive result in a germinal mouse test is sufficient to classify a chemical as a mammalian mutagen, regardless of the results in other tests. Such mouse tests are the specific-locus, dominant-skeletal, cataract, and heritable-translocation tests. 

For estimating the risk from dominant phenotypes, the Committee favors a dominant-mutation test in mice as most relevant to the human situation. If the risk is primarily chromosomal breakage, the heritable-translocation test is preferred. 

Newell, C. Sheu, and E. von Halle. Heritable translocation test in mice. Mutat. Res. 76 191-215, 1980. 

The heritable translocation test, although similar in some respects to the dominant lethal test, differs in that the offspring of the treated males are allowed to reach maturity and are thus available for C3ftologic determination of the type of chromosomal aberration inherited. In this assay treated males are mated weekly to different females over an 8 week period as is done in the domi-... 

Another method of monitoring heritable chromosomal abnormalities is the mouse sex chromosome-loss test. This assay differs from the dominant lethal test and heritable translocation test in that it is thought primarily to measure nondisjunctions. In this assay progeny of treated male and female mice are examined for sex-linked phenotypic differences. 

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