Estimation of genetic risks and increased incidence of genetic disease due to environmental mutagens.

In the estimation of the genetic hazards of environmental mutagens there are major problems in extrapolating from experimental data to human situations. Methods of overcoming these problems have been proposed, and may be achieved in the future. At present extrapolation can rarely be justified except where there are data on mutagenicity in germ cells of mammals. Where such data are available it is possible to estimate numbers of induced cases of genetic disease by making use of the principles and knowledge used in estimating genetic hazards of radiation, but the methods require modification. From experimental data the relative mutagenic effect (RME) of a compound may be obtained where the RME is defined as the ratio of induced mutation rate per unit dose to the spontaneous rate. From the RME and information on doses received environmentally a mutation index (MI) may be calculated where this is the product of the RME multiplied by dose and any relevant sensitivity factors. Tables may be prepared giving expected cases of genetic disease for known MI, and hence the effects of environmental exposures may be obtained. Some examples are shown for cytotoxic drugs.