16 3.2 Carcinogenicity and Adverse Health Effects Table 1 Carcinogenicity classification of PAHs and their derivatives. (not classifiable as to their carcinogenicity to humans, because of limited or inadequate experimental evidence) Epidemiological and animal experimental evidence on the health effects of air pollution has been growing and evolving. The International Agency for research on Cancer (IARC) has classified more than sixty PAHs and related compounds into four classes, carcinogenic to humans (Group 1), probably carcinogenic to humans (Group 2A), possibly carcinogenic to humans (Group 2B) and not classifiable as to their carcinogenicity to humans (Group 3). Among them, BaP is in Group 1. It is important that this classification is based on the evidence of carcinogenicity to humans, but does not depend carcinogenicity. Four on dibenz[a,h]anthracene, PAHs, dibenzo[a,l]pyrene, dibenz[a,j]acridine and one NPAH, 1-NP, are in Group 2A. Fifteen PAHs and hetero derivatives, such as Nap, benz[j]aceanthrylene, BaA, BbF, benzo[j]fluoranthene, dibenzo[a,h]pyrene, Chr, dibenzo[a,i]pyrene, IDP, benzofuran, dibenz[c,h]acridine and dibenz[a,h]acridine and five NPAHs, such as 5-NAc, 2-NF, 4-NP, 1,6- and 1,8-DNPs are in Group 2B. The other PAHs and NPAHs such as Fle, Pyr, 2-NP and 6-NBaP, are in Group 3, because of their limited or inadequate experimental evidence (Table 1). The IARC also classified PAH-containing materials, such as shale oils, coal-tar distillates, coal-tar pitch, coke, coal gasification products, indoor emissions from household combustion of coal, iron and steel founding products (occupational exposure), engine exhaust, diesel, outdoor air pollution, PM in outdoor pollution, soot (as found in the strength of the cyclopenta[cd]pyrene, BkF, 5-methylchrysene, benzo[c]phenanthrene, K. HAYAKAWA occupational exposure of chimney sweeps), tobacco smoke and second-hand tobacco smoke in Group 1 (IARC, 2021). It is thought that PAHs, NPAHs or OPAHs, which are contained in those materials, might contribute as causative damage. Epidemiological studies on adverse effects of these pollutants on lung function have been reported (Brucker et al., 2014; Mordukhovichi et al., 2016; Wang et al, 2016). PAHs are oxidized by ozone or nitrogen dioxide to produce QPAHs, OHPAHs or NPAHs in the atmosphere. They are adsorbed in the bronchi and alveoli to induce the production of ROS by the above metabolic pathway (Pitts et al., 1980; Pitts, 1983; Yoshikawa et al., 1985; Kumagai et al., 1997 and 2012; Hayakawa et al., 2007). Among PAHQs, ortho-QPAHs overproduce ROS and thereby significantly decrease cell viability, whereas para-QPAHs do not (Motoyama et al., 2009). ROS causes airway inflammation and exacerbation of asthma and allergies (Al-Daghri et. al., 2013; Anyenda et al., 2016; Zhao, 2022; Hara et al., 2022). Recently, the number of reports on non-genotoxic effects of OPAHs has been increasing: QPAHs and/or OHPAHs activate the aryl hydrocarbon receptor, additional nuclear receptors and intracellular signaling pathways. These facts suggest the possibility that OPAHs play an adverse role in the development, metabolism and growth of humans and animals and that more attention needs to be paid to the toxicities of PAH metabolites (Vondráček and Machala, 2021). oxidative DNA agents to

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