Nitro-aromatic compounds mutagenicity

The larger concern about nitro-aromatic compounds is that environmental exposure to these molecules can cause cancer in humans and in other living organisms. Nitro-aromatic compounds are acutely toxic, mutagenic, and carcinogenic in laboratory mammals and in vitro test systems [6, 8]. Despite the potential negative impact of nitro-aromatic compounds on human health, they continue to be emitted into ambient air from municipal incinerators [9], motor vehicles (particularly from diesel exhausts) [10, 11], industrial power plants [12], and other sources. Evidence... 

In what follows, no explicit attention is given to the specific type of assays or tester strains used to determine the mutagenic activity in nitro-aromatic compounds. This particular choice is made consciously, as the emphasis of this work is on the structural and electronic factors that modulate the mutagenic activity of the nitro-aromatic compounds in general. The interested readers are recommended to refer to the original works for more detailed discussions. 

The following section illustrates the key structural and electronic factors that play a role in the direct-acting mutagenicity of nitro-aromatic compounds. 

The position of the nitro group is also an important structural factor in determining the biological activity in nitro-aromatic compounds. This is evident from studies that show markedly different mutagenic potency in structural isomers of nitro-aromatic compounds [3,15, 24, 26, 30, 31,44,46]. Structural isomers like 1-, 2-, 3-, and 6-nitrobenzo[a]pyrene have dramatically different mutagenic potency [47—49] 6-nitrobenzo[a]pyrene is a weak mutagen, while 1-, 2-, and 3-nitrobenzo [a]pyrene are potent mutagenes [47 -9]. 

The structural arrangement and dimension can also influence the mutagenic potency of nitro-aromatic compounds. Vance and Levin studied the mutagenic potency of nitro-aromatic compounds in the naphthalenic and benzylic series... 

A QSAR model was developed to test the mutagenicity of 117 nitro-aromatic compounds in bacterial strain cells without metabolic activation [74]. It was shown that hydrophobicity plays a crucial role in determining the relative mutagenicity of most of the compounds studied. The mutagenicity of the nitro-aromatic compounds increases slowly at low logR and then decreases rapidly at high log P. It was suggested that a combination of adverse hydrophobic and steric effects could explain these observations. In a subsequent analysis, Debnath and Hansch [75]... 

The mutagenic activity (rev/yg) by linear regression analysis for the engine emission extracts and selected nitro-aromatic compounds is given in Table 2. Note that the commercially available 1-nitropyrene appears to be contaminated with di-nitropyrenes. 

Some of these N-, O-, and S-atom-functionalized polycyclic aromatic compounds (PACs) are powerful bacterial mutagens and animal, and possible human, carcinogens, e.g., the exocyclic nitro-substituted PAH 1-nitropyrene, VI, which is a primary pollutant in diesel exhaust (IARC, 1989). The endocyclic heterocyclic PAC dibcnz[fl,/ ]acridine, VII, is also classified as a possible human carcinogen (IARC, 1987 see Sections B and C). 

In the early 1990s, several nitro-polycyclic aromatic compounds that are powerful direct mutagens were identified in ambient particulate matter, including the nitrophenanthrene lactones 2- and 4-nitro-6//-dibenzo[6,r/]pyran-6-one, whose mutagenicities are given in Table 10.20. The 2-isomer (XI) is not only very... 

Tokiwa, H., R. Nakagawa, K. Morita, and Y. Ohnishi, Mutagenicity of Nitro Derivatives Induced by Exposure of Aromatic Compounds to Nitrogen Dioxide, Mutat. Res., 85, 195-205 (1981). 

However, it should be noted that even where kerosene heaters do not contribute significantly to particle mass concentrations, they may still be important in terms of health effects. This is because of the composition of the particles emitted, which include polycyclic aromatic compounds and other mutagenic species, as well as sulfate (Leaderer et al., 1990 Traynor et al., 1990). For example, Traynor et al. (1990) studied the emissions from unvented kerosene space heaters and identified a number of PAHs (naphthalene, phenanthrene, fluoranthene, anthracene, chrysene, and indeno[c,rf]pyrene) and nitro-PAHs (1-nitronaphtha-lene, 9-nitroanthracene, 3-nitrofluoranthene, and 1-nit-ropyrene), in addition to a host of other gaseous species. Baek et al. (1997) also reported increased levels of a number of gases indoors in homes and offices in Korea due to the use of kerosene heaters. 

Oxidation/hydroxylation of aromatic compounds by OH and HOONO is expected to enhance their degradation rate and hence decrease their lifetime on particulate matter, which in the case of pollutants is beneficial from the point of view of human health. Oxidation of PAHs could also lead to the production of photosensitizers such as quinones and aromatic carbonyls [10, 40, 41]. These compounds, if present in the gas phase, are also able to form aggregates and are therefore involved in the formation of secondary organic aerosol [42]. In contrast, nitration induced by OH + N02 or HOONO could lead to highly mutagenic nitro-PAHs [43] or phytotoxic nitrophenols [44, 45], in which case the health and environmental impact of the reaction intermediates is not negligible and is sometimes higher than that of the parent molecules. 

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