PAHs, noncarcinogenic

Figure 25.2 Ring structures of representative noncarcinogenic PAHs. (Modified from Lee and Grant 1981 Neff 1985.)...

A set of 200 PAH compounds were randomly selected from those stored for study. They fall into sixteen structural classes as shown in Table I. There are 73 carcinogens and 127 noncarcinogens in the set. 

This set of 28 descriptors supported linear discriminants that could completely separate 191 of the PAH s into the active and inactive classes. This is a recognition rate of 95.5 percent There are 66 carcinogens and 125 noncarcinogens in this set of compounds. 

The adequacy of the database for the aromatic EC>16-EC35 fraction, which consists of PAHs, is discussed in ATSDR (1995f). Data for suitable mixtures were not identified. Inhalation data for the individual constituents were particularly limited no MRLs were available. The oral data support the selection of a surrogate MRL for intermediate exposure to the noncarcinogenic constituents of this fraction, but it is uncertain whether this value is appropriate to represent the noncancer effects of the carcinogenic PAHs. 

Estimates of exposure levels posing minimal risk to humans (Minimal Risk Levels or MRLs) have been made for PAHs. An MRL is defined as an estimate of daily human exposure to a substance that is likely to be without an appreciable risk of adverse effects (noncarcinogenic) over a specified duration of exposure. MRLs are derived when reliable and sufficient data exist to identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration within a given route of exposure. MRLs are based on noncancerous health effects only and do not consider carcinogenic effects. MRLs can be derived for acute, intermediate, and chronic duration exposures for inhalation and oral routes. Appropriate methodology does not exist to develop MRLs for dermal exposure. 

Skin painting experiments ofa mixture of anthracene, chrysene, fluoranthene, phenanthrene, and pyrene were conducted on groups of 20 male C3H/HeJ mice (Warshawsky et al. 1993). Compounds dissolved in toluene were applied to shaved skin twice weekly for 6 months. Tumor incidence was determined at the end of the study. Treatment included solutions of a mixture of the five noncarcinogenic PAHs at 0.05 mg, or the same compounds in solution with 0.0005 mg benzo[a]pyrene, a dose known to be noncarcinogenic in a similar study design. Forthe mixture of the 5 PAHs at 0.05 mg each, administration alone produced papillomas and malignant tumors in 3 of 13 animals (23%), with a mean latency period of 73 weeks. With coadministration of benzo[a]pyrene, 8 of 17 (47%) had tumors (papillomas and malignant), with a mean latency period of 66 weeks. 

Carcinogenic PAHs have been suggested to have an effect on immune function (Luster and Rosenthal 1993 Saboori and Newcombe 1992), thereby allowing the induction of carcinogenesis, while noncarcinogenic PAHs do not affect immue function (see Section 2.4). The effects of dermally applied benzo[a]pyrene alone or following dermal pretreatment with the prostaglandin synthetase inhibitor, indomethacin, on contact hypersensitivity (cell-mediated immunity), production of antibodies to DNP (humoral immunity), and the induction of skin tumors was studied in male BALBc... 

Interactions between selected noncarcinogenic PAHs and carcinogenic benzo[a]pyrene have also been documented to reduce the carcinogenic potential of benzo[a]pyrene in animals. Benzo[a]fluoranthene, benzo[k]fluoranthene, chrysene, perylene, and a mixture of anthracene, phenanthracene, and pyrene significantly inhibited benzo[a]pyrene-induced injection-site sarcomas. However, other PAHs including anthracene, benzo[g,h,i]perylene, fluorene, and indeno[1,2,3-c,d]pyrene had no antagonistic effects (Falk et al. 1964). Coexposure of tracheal explants to benzo[e]pyrene and benzo[a]pyrene resulted in an increased incidence of tracheal epithelial sarcomas over that seen with either PAH alone (Topping et al. 1981). Phenanthrene administration with benzo[a]pyrene decreased the DNA adduct formation in mice (Rice et al. 1984). 

Benzo[a]pyrene and dibenz[a,h]anthracene in combination with 10 noncarcinogenic PAHs were less potent tumor-inducers than was dibenz[a,h]anthracene alone or in combination with benzo[a]pyrene. The noncarcinogenic or weakly carcinogenic PAHs include benzo[e]pyrene, phenanthrene, anthracene, pyrene, fluoranthene, chrysene, perylene, benzo[g,h,i]pyrene, and coronene. Dose-response relationships for tumor incidences were observed for benzo[a]pyrene and dibenz[a,h]anthracene either along or in combination with the 10 noncarcinogenic PAHs however, no treatment-related sarcoma incidences were observed for any of the 10 noncarcinogenic PAHs (Pfeiffer 1977). 

Phenanthrene, a noncarcinogenic PAH, demonstrated a dose-related inhibition of... 

Certain noncarcinogenic PAH and environmental contaminants Polyamine synthesis inhibitors (DMFO, retinoids)... 

Incineration ashes are used as fill material for roads and in construction.Municipal solid waste, mixed biofuel, and heating plant ashes were analyzed by Sohxlet extraction in toluene, deactivated silica gel cleanup, and GC-MS to show SPAHis levels of 140 to 77,000 /rg kg. The highest levels measured were for ashes from biofuels incineration with NAP and PHN as the predominant PAHs. Since volatile PAHs are lost in the Soxhlet sample preparation process, actual levels of NAP and PHN may have been underestimated. B[a]P ranged from 1 to 1327 /rg kg. Bottom ashes contained more of the less volatile PAHs as expected. Results for the mixed biofuel ash were in excess of the Swedish EPA soil limits for less sensitive land use of 7 /rgkg of carcinogens and 40 /rg kg for noncarcinogenic PAHs. 

Ring structures of representative noncarcinogenic PAHs. The numbering and lettering system for several PAHs is also given. Compounds are (1) naphthalene, (2) fluorene, (3) anthracene, (4) phenanthrene, (5) aceanthrylene, (6) benzo[a]fluorene, (7) benzo[b]fluorene,... 

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