Angela E. Auletta

Sister-chromatid exchange: second report of the Gene-Tox program

This paper reviews the ability of a number of chemicals to induce sister-chromatid exchanges (SCEs). The SCE data for animal cells in vivo and in vitro, and human cells in vitro are presented in 6 tables according to their relative effectiveness. A seventh table summarizes what is known about the effects of specific chemicals on SCEs for humans exposed in vivo. The data support the concept that SCEs provide a useful indication of exposure, although the mechanism and biological significance of SCE formation still remain to be elucidated.

The Salmonella typhimurium/mammalian microsomal assay: A report of the U.S. Environmental Protection Agency Gene-Tox Program☆

The Salmonella assay has been in use for almost 15 years and can be defined as a routine test for mutagenicity and for predicting potential carcinogenicity. It detects the majority of animal carcinogens and consequently plays an important role in safety assessment. The test is also routinely used as the frontline screen for environmental samples (complex mixtures) isolated from air, water and food. This role will continue to remain an area of growth as or because sample volumes associated with these testing areas are generally very limited and more extensive testing is generally impossible. While this test, like all others, has some limitations, it is recommended that it be regularly included in all genetic testing batteries.

Considerations in the U.S. Environmental Protection Agency's testing approach for mutagenicity

OPP: This paper provides the rationale and support for the decisions the OPP will make in requiring and reviewing mutagenicity information. The regulatory requirement for mutagenicity testing to support a pesticide registration is found in the 40 CFR Part 158. The guidance as to the specific mutagenicity testing to be performed is found in the OPPs Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: Human and Domestic Animals (referred to as the Subdivision F guideline). A revised Subdivision F guideline has been presented that becomes the current guidance for submitters of mutagenicity data to the OPP. The decision to revise the guideline was the result of close examination of the version published in 1982 and the desire to update the guidance based on developments since then and current state-of-the-science. After undergoing Agency and public scrutiny, the revised guideline is to be published in 1991. The revised guideline consists of an initial battery of tests (the Salmonella assay, an in vitro mammalian gene mutation assay and an in vivo cytogenetics assay which may be either a bone marrow assay for chromosomal aberrations or for micronuclei formation) that should provide an adequate initial assessment of the potential mutagenicity of a chemical. Follow-up testing to clarify results from the initial testing may be necessary. After this information as well as all other relevant information is obtained, a weight-of-evidence decision will be made about the possible mutagenicity concern a chemical may present. Testing to pursue qualitative and/or quantitative evidence for assessing heritable risk in relation to human beings will then be considered if a mutagenicity concern exists. This testing may range from tests for evidence of gonadal exposure to dominant lethal testing to quantitative tests such as the specific locus and heritable translocation assays. The mutagenicity assessment will be performed in accordance with the Agencys Mutagenicity Risk Assessment Guidelines. The mutagenicity data would also be used in the weight-of-evidence consideration for the potential carcinogenicity of a chemical in accordance with the Agencys Carcinogen Risk Assessment Guidelines. In instances where there are triggers for carcinogenicity testing, mutagenicity data may be used as one of the triggers after a consideration of available information. It is felt that the revised Subdivision F guideline will provide appropriate, and more specific, guidance concerning the OPP approach to mutagenicity testing for the registration of a pesticide. It also provides a clearer understanding of how the OPP will proceed with its evaluation and decision making concerning the potential heritable effects of a test chemical.(ABSTRACT TRUNCATED AT 400 WORDS)

Guide for the Salmonella typhimurium/mammalian microsome tests for bacterial mutagenicity

Since its development by Dr. Bruce Ames and his coworkers, the Salmonella typhimurium/mammalian microsome mutagenicity assay has been used widely throughout the world. Many authors have suggested various modifications and made recommendations in regards to this assay. Although the recommendations of a panel of experts was published in 1979 by de Serres and Shelby, a committee of members of the Environmental Mutagen Society (EMS) initiated this effort in response to the encouragement by the American Society of Testing and Materials (Committee E47.09.01) and because of new developments within the field of microbial mutagenesis testing. Its purpose is to provide a guide for people who perform or evaluate microbial mutagenesis tests, but it is not intended for these recommendations to replace or diminish the usefulness of presently available protocols and procedures.

1986 Survey of genetic toxicology testing in industry, government contract, and academic laboratories

SummaryResults of the 1986 Genetic Toxicology Associations survey of industrial, government, contract, and academic laboratories on the status of several assays in genetic toxicology are presented below.1.The most commonly used assay was the Salmonella typhimurium/mammalian microsomal (Ames) assay, which was used by 83% of all respondents.2.The next five (5) most commonly used assays were in vitro cytogenetics (72%), in vivo cytogenetics (59%), CHO HGPRT gene mutation (55%), the micronucleus assay (53%), and L517BY gene mutation (45%).3.The assay showing the greatest percentage increase in routine use was the micronucleus assay which went from 14% in 1984 to 34% in 1986, an increase of 20%.4.Other assays which increased in routine use were CHO HGPRT mutation (+18%); in vitro cytogenetics (+14%); L5178Y gene mutation (+9%), and the Ames assay (+5%).5.Routine use of in vitro UDS assays declined by 6%; use of in vitro SCE assays declined by 12%.6.There was no change in the rate of routine use of in vivo cytogenetics or in vivo SCE assays.7.Assays routinely performed on contract included the Salmonella assay, CHO HGPRT gene mutation, in vitro cytogenetics, in vitro UDS, in vivo cytogenetics, the micronucleus assay, L5178Y gene mutation, and the Drosophila sex-linked recessive lethal assay.8.Four assays were being developed by five or more laboratories. These included in vitro SCE (8); the micronucleus assay (7); in vivo SCE (6); and DNA adduct formation (5).9.A total of 17 assays had been abandoned by one or more laboratories. however, since no assay had been given up by more than three laboratories no conclusions can be drawn about the overall robustness of any of the assays on the survey form.