[en] Values of radiation equivalents of chemicals have been calculated for formaldehyde (FA) from detailed data on its genetic effects on yeast, Saccharomyces cerevisiae, and compared with the effects induced by gamma radiation. For the haploid yeast strain, 1 (mmol FA.ltr^-1).min (i.e. 1 mM FA.min) is equivalent to 9.6 rad, and for diploid yeast it is equivalent to 33 rad. These values are within the range of values calculated for E. coli and mammalian cells. Some major differences in the response to FA and radiation are encountered, depending upon the cellular physiological conditions, the genetic background and the degree of ploidy (haploid versus diploid) and growth phase (exponential versus stationary), among others. Difficulties encountered in the estimation of rad-equivalent values for specific chemicals and for defined biological end-points (e.g. rate of reverse mutation in the specific biochemical loci) are discussed. It is concluded that by exercising appropriate caution relating to the differences in the mechanisms of action of the chemical mutagens and radiations, meaningful rad-equivalent values could be estimated that could help express the comparative biological effects of chemicals in terms of radiation unit. (author)

[en] The present study deals with (1) the dose-response relationship of chromosome aberrations induced in bone-marrow cells and spermatogonia of ddY-SLC and C57BL/6J mice with cadmium chloride or 200 kV X-rays, and (2) a comparison of the relative biological effectiveness of these two agents. A linear dose-response curve was obtained from the bone-marrow cell experiment according to which the mutagenicity of cadmium chloride in terms of radiation equivalence was estimated as 1.75-7.00 mg CdCl₂ per kilogram body weight approximately equal to 50-100 R X-rays. For spermatogonia, the response was markedly different among the strains owing to differences of cadmium susceptibility of the strains. In susceptible ddY-SLC mice, permanent sterility was induced at a low dose of 1.75 mg/kg, but in resistant C57BL/6J mice no significant effects were detected either in fertility or in induction of chromosome aberrations in spermatogonia, and hence no consistent and reasonable estimation of radiation equivalence is available. (author)

[en] The radiation-equivalent concept has been supported as providing an effective and convenient approach towards a comparative evaluation of the genetic hazards from chemicals and radiations in a common language. The proposed unit of radiation equivalent is thus intended as a means of comparing chemically induced genetic effects with one another and with those of radiation. Since the biological end-effects are to be taken into consideration as the terms of reference, the details of the differences in their underlying mechanisms of action should not be a substantial hindrance to such a concept. Accordingly, different rad-equivalent values of chemicals are to be expected for different end-points of genetic damage, which further reflects some parallelism with radiations of different LET and the corresponding differences in the RBE values. Regarding the extrapolation of data from sub-mammalian systems to man in the risk assessment the need for exercising some caution is emphasized in view of the paucity of relevant information. (author)

[en] Most of the genetic effects induced by chemicals have their counterpart in the genetic effects induced by radiations. Also it is at the genetic level where mutagenic effects are expressed in human populations. Therefore, radiation dosimetry can be used as a standard for comparison if comparisons are made on one genetic parameter at a time. Comparative dosimetry will have to be made precise. Mutagenic efficiency, mutagenic effectiveness, species and dose-action kinetics will have to be taken into account for each compound tested. (author)

[en] The development of standards for the genetic risk evaluation of environmental chemical mutagens should be guided by the experience and information accumulated in mammalian radiation genetics. Measurement of specific-locus mutation rates and direct determination of the dominant skeletal mutations in mouse are recommended to provide the conceptual and calculative bases for such hazard assessment in man. For comparative risk evaluation of chemical mutagens in terms of the radiation dose the concept of relative mutagenic efficiency (RME) has been elaborated and applied. The RME of a chemical mutagen is expressed as the dose of ionizing radiation that is needed to induce the same mutation frequency as that induced by a chemical mutagen acting at its maximum mutation rate in the same test system. Based upon such a comparison of mutation rates induced by Mitomycin C and Natulan and of the specific-locus mutation frequency after irradiation of the same germ-cell stages, the following RME values have been obtained: 5.25 mg of Mitomycin C per kilogram body weight approximates 140-145 R and 600 mg of Natulan per kilogram body weight approximates 170-175 R. The limitations of the various assay systems, the resultant mouse data and the underlying genetic assumptions for extrapolation to man and for his risk evaluation are discussed. (author)

[en] The sense of an urgent need for risk evaluation of chemical mutagens and carcinogens in man's environment naturally tends to direct attention to the long-standing and successful experience in the field of radiation. Essential criteria for the interaction of chemical agents and radiation with biological systems are analysed and discussed. The marked dissimilarities in this regard between radiation and chemical agents provide the major limitations and hindrance to the meaningful interpretation of the chemical-induced effects in terms of radiation equivalents. (author)

[en] General considerations which make the concept of rad equivalence useful are reviewed, together with some data supporting this concept. A number of the potential difficulties are also considered. It is argued that forward mutation rates must be used and that the whole spectrum of genetic changes must be considered, but that with these qualifications the concept of radiobiological equivalence is useful for comparisons of the impact of chemicals and radiations, and for limitation of population exposures. (author)

[en] It is a difficult task to compare radiation with chemicals on the molecular level because there is only limited information on lesions which remain after DNA repair processes and which are responsible for late effects. Repair mechanisms, interaction of chemicals with DNA or DNA repair processes, as well as cellular model systems with and without excision repair are described. (author)

[en] The feasibility of applying the radiation health philosophy to comparative and collective risk assessment of environmental pollutants has been elaborated with mathematical formulations and computations for specific alkylating agents. Upon critical analysis there seems to be no major disagreement between the scientific arguments of the antagonists and protagonists of the radiation-quantitative equivalences of chemicals and ionizing radiation could be neutralized if suitable reaction-kinetically defined units (e.g. the rad equivalent), chemical tissue doses (as opposed to pharmacological doses), and the lower region of the respective dose-response curves were taken into consideration in such computations. The accuracy and reliability of the comparative risk estimate concept could be enhanced through more precise definitions of the rate constants, coefficients, critical nucleophilicity and the correction factors involved, through further work encompassing a wider range of chemicals interacting with the biological systems in the environment. (author)

[en] It is reasonably certain that the introduction or increase of pollutants in the environment can augment mutagenic and carcinogenic effects. These effects are operationally definable, but the genetic organization and the underlying mechanisms of DNA repair, mutagenesis and carcinogenesis are so complex as to make the extrapolation of results from mutagenicity test data to carcinogenicity somewhat uncertain. The subject is reviewed. Recent discoveries in gene organization and expression include overlapping genes in bacteriophages, split genes, processing of RNA and splicing, translocation of genes in eukaryotes, inactivation of the X-chromosome in mammals, etc. Apart from the genetic regulation, plasmids, insertion sequences and mutators can additionally affect mutation frequency. Cancers due to gene mutations, viruses, chemicals and physical agents are known. However, little is known about the epigenetic mechanisms involved. The value of mutagenicity test data is beyond question, but in view of the extraordinary complexities encountered our extrapolations will be more sound if the data have the underpinning of basic information. (author)