Use Of Short-term Tests Research Articles

Water, salt water, and alkaline solution uptake in epoxy thin films

ABSTRACTAs a means of characterizing the diffusion parameters of fiber reinforced polymer (FRP) composites within a relatively short time frame, the potential use of short term tests on epoxy films to predict the long‐term behavior is investigated. Reference is made to the literature to assess the effectiveness of Fickian and anomalous diffusion models to describe solution uptake in epoxies. The influence of differing exposure conditions on the diffusion in epoxies, in particular the effect of solution type and temperature, are explored. Experimental results, where the solution uptake in desiccated (D) or undesiccated (U) thin films of a commercially available epoxy matrix subjected to water (W), salt water (SW), or alkali concrete pore solution (CPS) at either 20 or 60°C, are also presented. It was found that the type of solution did not significantly influence the diffusion behavior at 20°C and that the mass uptake profile was anomalous. Exposure to 60°C accelerated the initial diffusion behavior and appeared to raise the level of saturation. In spite of the accelerated approach, conclusive values of uptake at saturation remained elusive even at an exposure period of 5 years. This finding questions the viability of using short‐term thin film results to predict the long‐term mechanical performance of FRP materials. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 1898–1908, 2013

Utility of a test for chromosomal malsegregation in Saccharomyces cerevisiae strain D61.M for the detection of antianeugens: test of the model combination of chlorophyllin and nocodazole

Despite the fact that aneuploidy is a major genetic cause of human morbidity and mortality, antimutagenicity studies have used predominantly short-term tests that detect gene mutations, chromosomal aberrations, and micronuclei. Therefore, the major deficiency in the use of short-term tests for antimutagenicity studies is those that detect chromosomal malsegregation leading to aneuploidy. Thus, we initiated a study on the utility of short-term tests for the detection of antianeugenic activity. We selected strain D61.M of Saccharomyces cerevisiae, nocodazole, and chlorophyllin as a model short-term test, aneugen, and antimutagen, respectively, for our initial study. Chlorophyllin strongly inhibited the aneugenic activity of nocodazole, but had no effect on the endpoints when tested alone, in strain D61.M. To our knowledge, this is the first report of an antianeugen. Furthermore, we conclude that strain D61.M can be used as a relatively simple, inexpensive, and rapid short-term test for the study of antianeugenicity.

Role of genotoxicity assays in the regulation of chemicals in The Netherlands: considerations and experiences

This paper discusses genotoxicity testing and data interpretation as applied in The Netherlands in the context of the regulation of chemicals. Guidelines were first formulated in 1981 and their use evolved in practice, on the basis of increasing experience at the national and international levels. The distinction between in vitro assays to detect intrinsic genotoxic properties and in vivo assays as a subsequent phase to show the realization of this potential in an intact organism has always been a cornerstone of the Dutch approach. Several critical aspects of the use of short-term genotoxicity tests in sequential schemes are discussed, such as their predictivity for carcinogenicity, the limited database concerning the performance of short-term in vivo assays, the relevance of devising separate strategies to test for possible carcinogenicity and germ cell mutagenicity, and the use of short-term tests to discriminate between genotoxic and non-genotoxic carcinogens. Examples are given of how short-term tests contributed to the toxicological evaluation of chemicals in The Netherlands.

Sperm evaluation in human genetic monitoring

Health hazards, including reproductive hazards, resulting from exposure to mutagenic chemical or physical agents are a major concern. Human genetic monitoring is a relatively new approach to the evaluation of human population exposure to mutagens that is based on the use of short-term tests with human cells (including sperm), tissues, and body fluids for genetic damage. Evaluation of sperm for count, percentage of morphologically abnormal forms, and frequency of heads containing zero, one, or two fluorescent bodies have been incorporated in genetic monitoring studies. In this paper, the application of human genetic monitoring to the evaluation of germ cell mutagen exposure is discussed. The purposes and limitations of human genetic monitoring studies are presented. Some of the practical issues involved in the use of sperm studies in genetic monitoring are described through the examples of two studies in different settings that were conducted by the author's laboratory. The first was a study of Autopsy Service workers within the resident institution of the laboratory. The second was a study of workers exposed to coal tar pitch volatiles at an industrial plant approximately 1,000 miles from the laboratory.

The use of short-term tests for the detection of genotoxic activity in body fluids and excreta

The use of short-term tests for the detection of genotoxic activity in body fluids and excreta

Successful use of short-term tests for academic purposes: Their use in identification of new environmental carcinogens with possible risk for humans

In the early 1970s, the short-term microbial mutation tests, particularly Ames' Salmonella test began to be used by workers in cancer research and environmental regulatory agencies (Ames, 1971; Ames et al., 1975; McCann et al., 1975). At that time, the public was much concerned with carcinogenesis resulting from pollution by chemical industries. Numerous new synthetic chemicals have been introduced into our environment and some of these were found to be carcinogenic to rodents and suspected to be carcinogenic to humans. These chemicals could not all be examined in long-term animal carcinogenesis experiments in rodents because of shortages of financial resources and more especially of qualified persons with the abifity to carry out the many necropsies and histological analyses required. So the introduction of short-term microbial mutation tests was very welcome in scientific circles. Earlier papers on the overlap of chemicals giving positive results for mutagenicity in short-term microbial mutation tests and showing carcinogenicity in long-term

Book Reviews: Current Issues in Toxicology. Interpretation and extrapolation of chemical and biological carcinogenicity data to establish human safety standards. The use of short-term tests for mutagenicity and carcinogenicity in chemical hazard evaluation. Edited by H. C. Grice. Springer-Verlag, Berlin, 1984, 197pp., DM52

Book Reviews: Current Issues in Toxicology. Interpretation and extrapolation of chemical and biological carcinogenicity data to establish human safety standards. The use of short-term tests for mutagenicity and carcinogenicity in chemical hazard evaluation. Edited by H. C. Grice. Springer-Verlag, Berlin, 1984, 197pp., DM52

Comments on the Carcinogenicity and Mutagenicity of metals and their compounds†

The carcinogenicity of metals has received extensive study, both epidemiologically and in the laboratory. These have included case reports of occasional human occurrence or clusters of cancer cases as well as extensive epidemiologic studies; in addition, there has been significant laboratory research on the whole animals and in vitro systems. This body of information will be examined selectively. I will not in this paper attempt a comprehensive review of the mutagenicity and carcinogenicity of metals and their compounds. Rather, I will attempt to set forth some historical perspectives, and to comment on some current gaps and needs. Other papers in this workshop have presented thorough and very current reviews of most of the topics briefly noted in this presentation and do not require repetition here. The cancer issue has been studied and reported on far more extensively than that relating to heritable mutations. There has been in recent years increasing interest in the use of short term tests for mutageni...

The use of short-term tests and limited bioassays in carcinogenicity testing

A brief discussion is given of the use of short-term in vivo and in vitro tests in carcinogenicity testing. Data are presented on the performance of nine such tests and five limited bioassays, as measured in terms of their sensitivity, specificity, accuracy, and predictive value. It is concluded that tests are available which, when used in combinations such as have been proposed by various authors, are capable of correctly identifying carcinogens and noncarcinogens with high confidence. A discussion of the statistics of batteries of tests is given. This is followed by a semiquantitative graphical representation and a discussion of how, on proceeding through a testing scheme such as that proposed by J. H. Weisburger and G. M. Williams (1981, Science 214, 401–407), the cumulative cost and the probability of correctly identifying a carcinogen or a noncarcinogen change as results become available from each of the stages of such a testing scheme.

Short-term tests in the framework of carcinogen risk assessment to man.

Short-term tests designed to detect possible carcinogenicity have been extensively refined during the last years. Presently, many more or less simple and convenient systems are available to detect mutations, chromosome effects, DNA damage, and malignant transformation. Although their relevance to carcinogenicity is often reasonably good, inconsistencies in the pattern of response indicate that their role as predictive indicators of carcinogenicity is still uncertain. The use of short-term tests in carcinogen risk assessment does seem feasible. These tests, however, should not be the only characteristic taken into consideration in such a risk assessment. Other characteristics such as chemical structure, biotransformation, and pharmacokinetics, qualitative and quantitative physiological and/or morphological effects, species, strain, and organ specificity, dose-response relation, and information on human studies, if available, are of importance too. Current knowledge does not permit a rigid classification of carcinogens, but does warrant a subclassification into genotoxic and nongenotoxic compounds. Whereas for genotoxic compounds a real threshold cannot be expected on a theoretical basis, the existence of a threshold may well be expected for nongenotoxic compounds. In conjunction with other characteristics it may then be decided whether a genotoxic or nongenotoxic compound may be or may not be permitted in the human environment. In this evaluation process it is anticipated that for genotoxic compounds other extrapolation systems should be used, as compared to nongenotoxic compounds, where in fact a conventional food toxicology safety factor may be applied. Short-term tests are very important in the subclassification with respect to genotoxicity and seem to be of value for the detection of promoter activity as well.

Use of short-term tests to detect genetic effects of complex mixtures of environmental interest

Use of short-term tests to detect genetic effects of complex mixtures of environmental interest

Energy-Related Pollutants in the Environment: Use of Short-Term Tests for Mutagenicity in the Isolation and Identification of Biohazards

In an effort to gather information on the potential genetic hazards of existing or proposed energy-generating or -conversion systems, we have begun a correlated analytical and genetic analysis of a number of technologies. The work is divided into two phases: one deals with known compounds expected to occur in the environment through energy production, conversion, or use; the other deals with actual samples from existing or experimental processes. To approach the problems of coping with and testing large numbers of compounds, we set up a form of the “tier system.” Operating units utilizing Salmonella, Escherichia coli, yeast, human leukocytes, mammalian cells, and Drosophila have been initiated. Various liquid-liquid extraction methods and column chromatographic separations have been applied to crude products and effluents from oil-shale, coal-liquefaction, and coal-gasification processes. Mutagenicity of the various fractions is assayed by means of reversion of histidine-requiring auxotrophs of Salmonella typhimurium; comparative studies are carried out with the other genetic systems. In order to incorporate metabolic activation of these fractions and compounds, rat liver homogenates (S-9) are used in the various assays. Results implicate chemicals occurring in the basic (ether-soluble) and the neutral fractions as potential genetic hazards. Chemical constituents of these fractions (identified or predicted) were tested individually for their mutagenic activity.

Energy-related pollutants in the environment: Use of short-term tests for mutagenicity in the isolation and identification of biohazards

In an effort to gather information on the potential genetic hazards of existing or proposed energy-generating or -conversion systems, we have begun a correlated analytical and genetic analysis of a number of technologies. The work is divided into two phases: one deals with known compounds expected to occur in the environment through energy production, conversion, or use; the other deals with actual samples from existing or experimental processes. To approach the problems of coping with and testing large numbers of compounds, we set up a form of the "tier system." Operating units utilizing Salmonella, Escherichia coli, yeast, human leukocytes, mammalian cells, and Drosophila have been initiated. Various liquid-liquid extraction methods and column chromatographic separations have been applied to crude products and effluents from oil-shale, coal-liquefaction, and coal-gasification processes. Mutagenicity of the various fractions is assayed by means of reversion of histidine-requiring auxotrophs of Salmonella typhimurium; comparative studies are carried out with the other genetic systems. In order to incorporate metabolic activation of these fractions and compounds, rat liver homogenates (S-9) are used in the various assays. Results implicate chemicals occurring in the basic (ether-soluble) and the neutral fractions as potential genetic hazards. Chemical constituents of these fractions (identified or predicted) were tested individually for their mutagenic activity.

The use of short-term tests to measure the preventive action of reducing agents on formation and activation of carcinogenic nitroso compounds

The effect of reducing agents on the nitrosation of methylguanidine (MG) and on the in vitro activation of dimethylnitrosamine (DMN) was examined by measuring DNA-repair synthesis (unscheduled incorporation of [ 3H]TdR). shifts in alkaline sucrose gradients, frequency of chromosome aberrations, and clone-forming capacity of cultured human fibroblasts. The reducing agents examined were sodium ascorbate, cysteine, cysteamine, and propyl gallate. Since the short-term bioassays used can be quantitated, it has become relatively easy to detect the inhibitory action of reducing compounds on the nitrosation reaction of MG and metabolic activation (with S-9 preparation) of the precarcinogen DMN, to measure their effective dose range, and to establish the most effective ratios between inhibitory agent and reactant. The results indicate that DNA-repair synthesis is a suitable short-term test for studying the numerous combinations and permutations between several carcinogenic or non-carcinogenic agents, and for estimating the capacity of inhibitory agents to affect formation and activation of chemical carcinogens.

The use of short-term tests to measure the preventive action of reducing agents on formation and activation of carcinogenic nitroso compounds

The effect of reducing agents on the nitrosation of methylguanidine (MG) and on the in vitro activation of dimethylnitrosamine (DMN) was examined by measuring DNA-repair synthesis (unscheduled incorporation of [ 3H]TdR), shifts in alkaline sucrose gradients, frequency of chromosome aberrations, and clone-forming capacity of cultured human fibroblasts. The reducing agents examined were sodium ascorbate, cysteine, cysteamine, and propyl gallate. Since the short-term bioassays used can be quantitated, it has become relatively easy to detect the inhibitory action of reducing compounds on the nitrosation reaction of MG and metabolic activation (with S-9 preparation) of the precarcinogen DMN, to measure their effective dose range, and to establish the most effective ratios between inhibitory agent and reactant. The results indicate that DNA-repair synthesis is a suitable short-term test for studying the numerous combinations and permutations between several carcinogenic or non-carcinogenic agents, and for estimating the capacity of inhibitory agents to affect formation and activation of chemical carcinogens.

Evaluation of Chromosome Aberration Effects of Chemicals on Mouse Germ Cells

Research ArticleOpen AccessEvaluation of chromosome aberration effects of chemicals on mouse germ cells. W M Generoso W M Generoso Search for more papers by this author Published:1 December 1973https://doi.org/10.1289/ehp.730613Cited by:15AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited By Garcia-Sagredo J (2008) Fifty years of cytogenetics: A parallel view of the evolution of cytogenetics and genotoxicology, Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, 10.1016/j.bbagrm.2008.05.003, 1779:6-7, (363-375), Online publication date: 1-Jun-2008. Lockhart A, Piegorsch W and Bishop J (1992) Assessing overdispersion and dose-response in the male dominant lethal assay, Mutation Research/Environmental Mutagenesis and Related Subjects, 10.1016/0165-1161(92)90007-9, 272:1, (35-58), Online publication date: 1-Aug-1992. Kligerman A (1982) Fishes as Biological Detectors of the Effects of Genotoxic Agents Mutagenicity, 10.1016/B978-0-12-336180-6.50020-X, (435-456), . Brusick D, Matheson D, Jagannath D, Braude M, Brockman H and Hung C (2008) Genetic Screening of Compounds used in Drug Abuse Treatment. II. Methadone, Drug and Chemical Toxicology, 10.3109/01480548109066368, 4:1, (1-18), Online publication date: 1-Jan-1981. Sykora I, Gandalovičovǎ D and Řezábek K (1979) Absence of noxious effects of selected neuroleptics in dominant-lethal mutagenesis assay, Mutation Research/Genetic Toxicology, 10.1016/0165-1218(79)90090-9, 66:3, (291-299), Online publication date: 1-Mar-1979. Reddy C, Chan P and Hayes A (1978) Teratogenic and dominant lethal studies of patulin in mice, Toxicology, 10.1016/S0300-483X(78)91339-2, 11, (219-223), Online publication date: 1-Jan-1978. Ong T (1978) Genetic activities of hycanthone and some other antischistosomal drugs, Mutation Research/Reviews in Genetic Toxicology, 10.1016/0165-1110(78)90012-X, 55:1, (43-70), Online publication date: 1-Jan-1978. Wiemann H and Lang R (1978) Strategies for detecting heritable translocations in male mice by fertility testing, Mutation Research/Environmental Mutagenesis and Related Subjects, 10.1016/0165-1161(78)90004-3, 53:3, (317-326), Online publication date: 1-Jun-1978. Brusick D, Matheson D, Jagannath D, Braude M and Brockman H (2008) Genetic Screening of Compounds Used in Drug Abuse Treatment I. Naltrexone Hydrochloride, Drug and Chemical Toxicology, 10.3109/01480547809034430, 1:2, (103-135), Online publication date: 1-Jan-1978. Sheu C, Moreland F, Oswald E, Green S and Flamm W (1978) Heritable translocation test on random-bred mice after prolonged triethylenemelamine treatment, Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 10.1016/0027-5107(78)90028-3, 50:2, (241-250), Online publication date: 1-May-1978. Brusick D (2018) Alteractions of germ cells leading to mutagenesis and their detection, Environmental Health Perspectives, 24, (105-112), Online publication date: 1-Jun-1978.Epler J, Larimer F, Rao T, Nix C and Ho T (2018) Energy-related pollutants in the environment: Use of short-term tests for mutagenicity in the isolation and identification of biohazards, Environmental Health Perspectives, 27, (11-20), Online publication date: 1-Dec-1978. Matter B (1976) Problems of testing drugs for potential mutagenicity, Mutation Research/Environmental Mutagenesis and Related Subjects, 10.1016/0165-1161(76)90149-7, 38:4, (243-258), Online publication date: 1-Aug-1976. Kalter H (1975) Some relations between teratogenesis and mutagenesis, Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 10.1016/0027-5107(75)90041-X, 33:1, (29-36), Online publication date: 1-Nov-1975. Flamm W (1974) A tier system approach to mutagen testing, Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 10.1016/S0027-5107(74)80030-8, 26:4, (329-333), Online publication date: 1-Aug-1974. Vol. 6December 1973Metrics About Article Metrics Publication History Originally published1 December 1973Published in print1 December 1973 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.