Cancer risk assessment for oral exposure to PAH mixtures

Abstract

Cancer risk estimates for oral uptake of polycyclic aromatic hydrocarbons (PAHs) currently are based on risk estimates for benzo[a]pyrene (BAP). The potency of PAH mixtures often is calculated using relative potency values (BAP equivalency factors). We used recent oral carcinogenicity studies with BAP and coal tar mixtures, as well as older studies for a critical reappraisal of the current practice. A literature survey identified several carcinogenicity studies with oral and dermal exposure and lung implantation that allow a direct comparison of the carcinogenic potency of pure BAP and PAH mixtures. Moreover, when the PAH composition of the mixture has been analysed, prediction of the potency of PAH mixtures by BAP equivalency factors could be compared with the observed PAH potency. The analysis indicates that BAP equivalency factors do not describe adequately the potency of PAH mixtures and lead to underestimations of carcinogenic potency in most cases. Evaluation of several studies with various PAH mixtures revealed that the potency ratio between pure BAP and the PAH mixture in the same assay is highly dependent on the exposure pathway and the target organ, therefore potency estimates for PAH mixtures should be derived separately for oral, dermal and inhalative exposure using data from studies with the relevant pathway. A cancer slope factor for oral PAH exposure was derived based on data from a recent feeding study with coal tar mixtures. By using incidence data for all exposure-related tumours, a slope factor for humans of 11.5 (human excess risk per oral lifetime exposure with 1 mg BAP kg(-1)day(-1) in a PAH mixture) was obtained. Our analysis led to the conclusion that the contribution of BAP to the carcinogenic potency of the mixture depends on the exposure pathway and type of cancer observed but is relatively constant for various PAH mixtures from industrial sources. Thus, the derived oral slope factor is recommended to be used for the risk assessment of PAH-contaminated soils.

Carcinogenic polycyclic aromatic hydrocarbon‐DNA adducts and mechanism of action

“…This is a trend that may be observed with other mixtures (Fig. 4) [DeutschWenzel et al, 1984;Grimmer et al, 1987;Weyand et al, 1995;Culp et al, 1998;Mangelsdorf et al, 1998;Schneider et al, 2002]. These idiosyncrasies point to factors contributing to PAH-induced carcinogenesis beyond DNA-binding ability.…”

“…The mixtures in these studies from top to bottom included diesel automobile exhaust condensate, flue gas condensate, coal tar product 2, coal tar product 1, manufactured gas plant residue in lung, manufactured gas plant residue in forestomach, coal tar mixture 2 and coal tar mixture 1 in lung, and coal tar mixture 2 and coal tar mixture 1 in forestomach [Deutsch-Wenzel et al, 1984;Grimmer et al, 1987;Weyand et al, 1995;Culp et al, 1998;Mangelsdorf et al, 1998;Schneider et al, 2002]. Adapted from Schneider et al [2002]. ' 2002 John Wiley and Sons Ltd. Reproduced with permission.…”

Polycyclic aromatic hydrocarbons (PAH) in Danish barbecued meat

“…For 33 risk assessed PAH compounds, 15 showed genotoxic and carcinogenic effects (EFSA, 2008;SCF, 2002). Of these, benzo[a]pyrene (BaP) is the most commonly studied and has shown various toxicological effects in experimental animals, with the most critical effects being genotoxicity and cancer (SCF, 2002;Schneider, Roller, Kalberlah, & Schumacher-Wolz, 2002). In 2004, BaP was introduced as a marker of the carcinogenic PAH in food with maximum limits in certain foods in the European Union (European Commission, 2006).…”

Levels, fingerprint and daily intake of polycyclic aromatic hydrocarbons (PAHs) in bread baked using wood as fuel

“…They may be regarded as potentially genotoxic and carcinogenic to humans; their carcinogenicity depends on their structure (bay region) [31][32][33]. Toxicological investigations showed different carcinogenic potency for various PAHs-mixtures [34][35][36]. Very mutagenic and carcinogenic is B[a]P and it has been accepted as a marker of carcinogenic PAHs in food and environmental samples [37,38].…”