Benzol ölpyrene

Not only is it interesting toxicologically, it has a unique structure with a highly localized double bond between the carbon atoms 3 and 4 in the cyclopenta ring.

Analogous to acenaphthylene (Tables 10.1 and 10.36 and Sections E and F), this provides a reactive site for attack by ozone and OH and NO, radicals (see Eisenstadt and Gold, 1978; Sangaiah and Gold, 1985; Goldring et al., 1988; and Zielinska et al., 1988a). This is consistent with its rapid decay during transport as observed, for example, by Nielsen (1988) in Denmark, by Greenberg (1989) at three urban sites in New Jersey, and by Fraser et al. (1998) at four sites in southern California. See discussion in Box 10.10.

The human cell mutagenicities of several mono- and dinitropyrenes were determined by Busby and coworkers (1994b) in a forward mutation assay using a metabolically competent line of MCL-5 cells. Minimum detectable mutagen concentrations (MMC, in nmol ml-1; the smaller the detectable concentration, the greater the potency) were as follows: f ,6-dinitropyrene, 0.8; 1,8-dinitropyrene, 1.5; 4-nitropyrene, 3.1; 1-nitro-pyrene, 9.1. Other PACs tested, 2-nitropyrene, 1,3-dinitropyrene, and pyrene, were nonmutagens in this assay. There was an 11-fold range from the most (1,6-DNP) to the least (f-NP) potent mutagen.

In 1997, Busby and co-workers reported that 2-nitrofluoranthene, an important product of atmospheric transformations (vide infra) was inactive in MCL-5 cells but a potent mutagen in hlAlv2 cells; another important atmospheric reaction product, the nitrophenanthrene lactone 2-nitrodibenzopyranone (XI), was inactive in both hlAfv2 and MCL-5 cells. Furthermore, it was nonmutagenic in the forward mutation bacterial assay in the absence of rat liver postmi-tochondrial supernatant (— S9) but was mutagenic with the addition of S9 mix.

However, Sasaki and co-workers (1997b) reported that this nitro-PAH lactone is mutagenic in the MCL-5, and possibly the hlAlv2, human cell assays (Arey, personal communication), and it is a powerful direct-acting mutagen in the Salmonella reversion bacterial assay, e.g., 58,600 rev/nmol, TA98, — S9 (see Table 10.20, Arey et al. (1992), and Arey (1998a), and references therein). Additionally, DNA adducts have been found in the liver DNA from rats treated with this common air pollutant (Watanabe et al., 1996). 2-Nitronaphthalene, a volatile atmospheric reaction product of naphthalene (Sasaki et al., 1997a; Feilberg et al., 1999a), present in relatively high concentrations in ambient air (Gupta et al., 1996), is also genotoxic in the MCL-5 line of human cells (Sasaki et al., 1997b).

Busby and co-workers (1995) compared the mutagenicities of BaP and five dibenzopyrenes in the Salmonella typhimurium TM677 forward mutation bacterial assay (+ PMS) to three in the MCL-5 human cell assay. The powerful carcinogen dibenzo[a,/]pyrene was 50 times more potent than BaP in human cells (vide supra); however, it was only 1.7 times as potent as BaP in the bacterial assay. Interestingly, there was a 10,000-fold range between the most and least mutagenic PAH in MCL-5 human cells vs a range of only ~4 in the bacterial cells.

Durant et al. (1996, 1998) reported that several nitroarenes, e.g., 2-nitrofluoranthene, were less mutagenic than BaP in the hlAlv2 cell line and concluded, "For these compounds to be important hlAlv2 cell mutagens, their concentrations would need to be in the order of ~f pg/g or higher." Although Durant and coworkers did not detect 2-nitrofluoranthene in SRM 1649, Arey and co-workers (1988b) reported levels of 2-nitrofluoranthene as high as 10 yu-g/g in samples of ambient air from Claremont, California, ~60 km east of Los Angeles. Furthermore, it has been found in airsheds throughout the world (e.g., see Atkinson and Arey, 1994; Legzdins et al., 1994; Ciccioli et al., 1996; Hannigan et al., 1997; Fraser et al., 1998; and Arey, 1998a). Thus, 2-nitrofluoranthene may make a contribution to the hlAlv2 human cell mutagenicity of res-

pirable particles in ambient air, not only in the Los Angeles area but also at many other sites as well.

The toxicology-based conclusion that the minimum concentration for 2-nitrofluoranthene to be an important human cell mutagen is 1 p-g/g, coupled with air quality sampling data showing its concentrations in respirable particles sampled from ambient air can in fact reach 10 ¡xg/g, provides a useful example of a productive symbiotic interaction between atmospheric chemists and toxicologists. Such interactions are essential for reliable risk assessments of air pollution and human health effects of complex combustion-generated mixtures of gases and particles.

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