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.

Investigation of the state of the science on combined actions of chemicals in food through dissimilar modes of action and proposal for science-based approach for performing related cumulative risk assessment 1Prepared by: Andreas Kortenkamp (ULSOP), Richard Evans (ULSOP), Michael Faust (F+B), Fritz Kalberlah (FoBiG), Martin Scholze (ULSOP), Ulrike Schuhmacher-Wolz (FoBiG)

No abstract

No abstract

Semipolar polycyclic aromatic compounds (sPACs) are frequently found in association with homocyclic polycyclic aromatic hydrocarbons (PAHs) in substances of unknown or variable composition, complex reaction products, or biological materials (UVCBs) from coal or crude oil and products derived thereof. However, major information deficiencies exist with regard to their prevalence and their toxicological and ecotoxicological potential, persistency, and bioaccumulation characteristics. Therefore, in this work, the environmental concern and relevance of sPACs was addressed in a general, stepwise approach. First, a large list of sPACs was collected and subsequently refined by assessing their persistence, bioaccumulation, and toxicity (PBT) properties by quantitative structure-activity relationship (QSAR) methods and their relevance by determining their respective frequency of occurrence. In this way, 15 priority sPACs were identified. These 15 priority sPACs were further characterized in detail with respect to their ecotoxicological properties, environmental behavior, carcinogenicity, and genotoxicity attributes. All of these 15 substances were quantified in distillate or product samples. In the next step, some principles for nomination of indicator substances, indicative for the overall content of sPACs, are derived. Data gaps on ecotoxicological endpoints preclude final conclusions, but the respective necessary supplemental tests were identified. Five of the 15 sPACs were tentatively characterized as potential substances of very high concern (SVHC) for the environment. The overall results of this study also clearly show that regulatory risk management of homocyclic PAHs within the European Regulation on Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) does not address the environmental concern created by sPACs within UVCBs from coal or crude oil. The study proves the need for additional regulatory steps under REACH and suggests indicator substances for their enforcement.

No abstract

No abstract

No abstract