Aromatic Amino and Nitro–Amino Compounds and their Halogenated Derivatives

Abstract

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 and mutagens and/or hemotoxicants 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 ‐toludine) 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 have been published. 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 seven subgroups of structurally related compounds.

Mechanistic QSAR of aromatic amines: New models for discriminating between homocyclic mutagens and nonmutagens, and validation of models for carcinogens

“…Out of 1,646 uniquely defined chemical structures, the most represented classes are aromatic amines (n 5 115), halogenated aliphatics (n 5 113), nitroaromatic compounds (n 5 42), and aliphatic aldehydes (n 5 33) [Benigni et al, 2007]. In a previous analysis, we found that about one fourth (200 out of 800) of the chemicals in a database of experimental carcinogenicity results collected in our laboratory were aromatic amines [Benigni, 2005].Many aromatic amines have been reported to be powerful carcinogens and mutagens, and/or hemotoxicants [Lai et al, 1996;Sugimura, 1997;Vineis and Pirastu, 1997;Skog et al, 1998], and have been studied experimentally [Woo and Lai, 2001]. To exert their carcinogenic potential, the aromatic amines have to be metabolized to reactive electrophiles.…”

Mechanistic QSAR of aromatic amines: New models for discriminating between homocyclic mutagens and nonmutagens, and validation of models for carcinogens

“…Out of 1,646 uniquely defined chemical structures, the most represented classes are aromatic amines (n 5 115), halogenated aliphatics (n 5 113), nitroaromatic compounds (n 5 42), and aliphatic aldehydes (n 5 33) [Benigni et al, 2007]. In a previous analysis, we found that about one fourth (200 out of 800) of the chemicals in a database of experimental carcinogenicity results collected in our laboratory were aromatic amines [Benigni, 2005].Many aromatic amines have been reported to be powerful carcinogens and mutagens, and/or hemotoxicants [Lai et al, 1996;Sugimura, 1997;Vineis and Pirastu, 1997;Skog et al, 1998], and have been studied experimentally [Woo and Lai, 2001]. To exert their carcinogenic potential, the aromatic amines have to be metabolized to reactive electrophiles.…”

Flexible use of qsar models in predictive toxicology: A case study on aromatic amines

“…The mechanistic rationale for the presence of MR in Eq. (1) is that steric bulk on the aromatic ring prevents enzymatic access and formation of the reactive intermediates (for a more detailed discussion on the mechanisms of action of the aromatic amines and how they relate to QSAR models, see Woo and Lai [2001], Benigni and Passerini [2002], Franke et al [2010], Benigni and Bossa [2011]). Table I and the accompanying Chart 1 provide some factual examples of the relationship between physical chemical factors and biological activity.…”

Recall and detection rates in screening mammography

“…The mechanistic rationale for the presence of MR in Eq. (1) is that steric bulk on the aromatic ring prevents enzymatic access and formation of the reactive intermediates (for a more detailed discussion on the mechanisms of action of the aromatic amines and how they relate to QSAR models, see Woo and Lai [2001], Benigni and Passerini [2002], Franke et al [2010], Benigni and Bossa [2011]).…”

Mechanistic QSAR of aromatic amines: New models for discriminating between homocyclic mutagens and nonmutagens, and validation of models for carcinogens

“…Out of 1,646 uniquely defined chemical structures, the most represented classes are aromatic amines (n 5 115), halogenated aliphatics (n 5 113), nitroaromatic compounds (n 5 42), and aliphatic aldehydes (n 5 33) [Benigni et al, 2007]. In a previous analysis, we found that about one fourth (200 out of 800) of the chemicals in a database of experimental carcinogenicity results collected in our laboratory were aromatic amines [Benigni, 2005].Many aromatic amines have been reported to be powerful carcinogens and mutagens, and/or hemotoxicants [Lai et al, 1996;Sugimura, 1997;Vineis and Pirastu, 1997;Skog et al, 1998], and have been studied experimentally [Woo and Lai, 2001]. To exert their carcinogenic potential, the aromatic amines have to be metabolized to reactive electrophiles.…”

Flexible use of qsar models in predictive toxicology: A case study on aromatic amines

“…The mechanistic rationale for the presence of MR in Eq. (1) is that steric bulk on the aromatic ring prevents enzymatic access and formation of the reactive intermediates (for a more detailed discussion on the mechanisms of action of the aromatic amines and how they relate to QSAR models, see Woo and Lai [2001], Benigni and Passerini [2002], Franke et al [2010], Benigni and Bossa [2011]). Table I and the accompanying Chart 1 provide some factual examples of the relationship between physical chemical factors and biological activity.…”

Recall and detection rates in screening mammography

“…The mechanistic rationale for the presence of MR in Eq. (1) is that steric bulk on the aromatic ring prevents enzymatic access and formation of the reactive intermediates (for a more detailed discussion on the mechanisms of action of the aromatic amines and how they relate to QSAR models, see Woo and Lai [2001], Benigni and Passerini [2002], Franke et al [2010], Benigni and Bossa [2011]).…”

Mechanistic QSAR of aromatic amines: New models for discriminating between homocyclic mutagens and nonmutagens, and validation of models for carcinogens

“…Out of 1,646 uniquely defined chemical structures, the most represented classes are aromatic amines (n 5 115), halogenated aliphatics (n 5 113), nitroaromatic compounds (n 5 42), and aliphatic aldehydes (n 5 33) [Benigni et al, 2007]. In a previous analysis, we found that about one fourth (200 out of 800) of the chemicals in a database of experimental carcinogenicity results collected in our laboratory were aromatic amines [Benigni, 2005].Many aromatic amines have been reported to be powerful carcinogens and mutagens, and/or hemotoxicants [Lai et al, 1996;Sugimura, 1997;Vineis and Pirastu, 1997;Skog et al, 1998], and have been studied experimentally [Woo and Lai, 2001]. To exert their carcinogenic potential, the aromatic amines have to be metabolized to reactive electrophiles.…”

Flexible use of qsar models in predictive toxicology: A case study on aromatic amines

“…The mechanistic rationale for the presence of MR in Eq. (1) is that steric bulk on the aromatic ring prevents enzymatic access and formation of the reactive intermediates (for a more detailed discussion on the mechanisms of action of the aromatic amines and how they relate to QSAR models, see Woo and Lai [2001], Benigni and Passerini [2002], Franke et al [2010], Benigni and Bossa [2011]). Table I and the accompanying Chart 1 provide some factual examples of the relationship between physical chemical factors and biological activity.…”

Recall and detection rates in screening mammography

“…The mechanistic rationale for the presence of MR in Eq. (1) is that steric bulk on the aromatic ring prevents enzymatic access and formation of the reactive intermediates (for a more detailed discussion on the mechanisms of action of the aromatic amines and how they relate to QSAR models, see Woo and Lai [2001], Benigni and Passerini [2002], Franke et al [2010], Benigni and Bossa [2011]).…”