Aromatic Amino and Nitro–Amino Compounds and Their Halogenated Derivatives

Aromatic amines are organic compounds that contain at least one amino group attached directly to an aryl moiety. Aromatic amines represent one of the most important classes of industrial and environmental chemicals. Many aromatic amines have been shown to be potent carcinogens, mutagens, skin sensitizers, and/or hematotoxicants capable of inducing methemoglobinemia. Since the introduction of substituted anilines and naphthylamines as intermediates for the manufacture of azo dyes in the mid-1800s, aromatic amines have found numerous uses in various industries. Substantial worker exposure to aromatic amines with subsequent induction of bladder cancer occurred before preventive measures were instituted. Beyond occupational exposure, humans may also be exposed to aromatic amines through environmental sources. At least three carcinogenic aromatic amines (4-aminobiphenyl, 2-naphthylamine, and o-toluidine) have been detected in cigarette smoke. Many commonly used pharmaceuticals contain or are aromatic amines. Owing to their hazard potential, aromatic amines have been the subject of many biomonitoring studies, making them model compounds in molecular dosimetry and epidemiology studies. Since extensive information is available on the metabolic pathways and, to a lesser extent, the mechanism(s) of action, aromatic amines have also become targets for genetic polymorphism studies with ultimate goals of identifying susceptible subpopulations and designing of strategies for cancer prevention and intervention. The multifaceted interest in aromatic amines has continued to attract a tremendous amount of scientific studies and attention. Since the publication of the previous edition of Patty's on aromatic amines, many reviews and important research articles on aromatic amines and halogenated nitroaromatics have been published. In addition, a number of heterocyclic aromatic amines have attracted increasing attention as carcinogens of environmental significance. In this chapter, we present an overview of the aromatic amine class as a whole with emphasis on recent studies, followed by an updated description on individual chemicals grouped into eight subgroups of structurally related compounds. Keywords: Aromatic amino compounds; carcinogenicity; halogenated derivatives; hemoglobin binding; mechanism of action; methemoglobinemia; mutagenicity; nitro–amino compounds; skin sensitization; teratogenicity