Amino- and nitroderivatives of benzene are widely used in the chemical industry as intermediate products in the production of dyes, medicines, pesticides, etc. For providing safety to people, which have contact with the amino- and nitroderivatives of benzene, it is necessary to study not only the acute and chronic toxicity of these substances, but also the long-term effects, for example embryotoxic effect. Our own studies, and studies of other authors, showed that under conditions of inhalation exposure for 4 hr/day 7 days/week throughout gestation of the Wistar rats such compounds as 2-nitro-4-bromophenol, the 3-nitrobenzoic acid, 3,4-difluoronitrobenzene, 3,4-difluoroaniline, ortho-phenylene diamine, 2,4- dinitroaniline, nitrobenzene, 2,4-dichloronitrobenzene and some others expressed an embryotoxic effect. This effect appeared as increased embryo losses, teratogenicity, changes in the central nervous system, the cardiovascular system, and changes in the physical development of progeny. In this case the Lowest Observed Adverse Levels (LOAELs) for embryotoxic effect were established at the lower levels than the LOAELs for maternal toxicity in pregnant dams. On the basis of using the Quantitative Structure-Activity Relationship (QSAR) analysis, the equations for prediction of both the LOAELs for maternal toxicity and for embryotoxic effects of amino- and nitroderivatives of benzene were obtained. This gives a possibility of approximate determination of the toxic effect of amino- and nitroderivatives of benzene (including embryotoxicity) at the stage of compound rational design even before its synthesis. Thus, in our opinion the occupational amino- and nitroderivatives of benzene may be potent embryotoxic agents, which is necessary to consider during the evaluation of permissible levels of exposure.
