(667f) Risk Characterization of Polycyclic Aromatic Hydrocarbons Based on Human Biomonitoring Data

The purpose of this study was to describe and evaluate the risk assessment for polycyclic aromatic hydrocarbons (PAHs). This included the construction and analysis of exposure scenarios in order to calculate expected relevant biomarker levels (e.g 1-OH-Pyrene concentration in urine and blood), which were directly compared with real life human biomonitoring (HBM) data. 1-OH-Pyrene was used as biomarker as a good correlation between 1-OH-Pyrene in urine and Benzo[a]Pyrene or total PAHs in air is confirmed. 1-OH- Pyrene is a pyrene metabolite and is therefore an indirect marker of exposure to PAH mixtures that include BaP. Towards this goal, exposure estimates for PAHs were calculated using the integrated exposure modelling platform INTEGRA and were later validated with HBM data. The assessment of 1-OH-Pyrene intake included major exposure pathways for the general population such as food and water, inhalation, dust and soil ingestion. The contribution of smoking and food in smokers present the same magnitude. In the occupational setting, exposure to PAHs mainly occurs through inhalation and also through dermal route. The HBM data, collected in the framework of several studies and facilitated by the HBM4EU consortium in an effort to cover a large part of EU Member states, were aggregated and age differentiated. HBM data were accompanied by detailed exposure related to environmental emissions data, food items residues concentration in dust and in soil, concentration in ambient and indoor air, were used as ancillary data for exposure reconstruction, describing multi-pathway and multi-route exposure.

Exposure reconstruction, a process of corresponding HBM data to external exposure, uses deterministic methods such as the intake mass balance and stochastic methods such as exposure conversion factor and Bayesian approach. This methodology is able to approximate the daily intake and to address complex exposure scenarios, dynamic in time. The HBM data have been selected since they pose a very good approximation of aggregate exposure, providing an integrated overview of the body burden to xenobiotics that an individual is exposed to. The risk characterization for PAHs was based on the Excess Life Cancer time Risk (ELCR) that was calculated using a dose-response relationship that utilize the cumulative exposure of B[a]P and transforms the occupational exposure to continuous exposure for the general population for a period of 70 years. According to that results, the regulatory threshold values for ELCR were found to be in between 10^-6 and 10^-4, where 10^-6 represents virtual safety, while 10^-4 represents high risk.

The exposure reconstruction results of the study can be considered representative for the general population in the EU from newborns to the elderly. The modelled data showed that diet is the main source of pyrene exposure for all age groups. The daily intake for all age groups ranges between 0.16 and 0.5 μg/kg_bw/d with a mean daily dietary intake of 0.35 μg/kg_bw/d. Infants and toddlers are susceptible to PAHs exposure through soil and dust ingestion originating by the increased object to mouth activity presenting a daily intake of 0.003 μg/kg_bw/d for these two pathways of exposure. Regarding to HBM data, the levels of 1-OH-Pyrene in urine are in the range of 0.1 to 1 mg/L. The daily intake of pyrene based on the HBM data was estimated to be in the range of 0.004 to 0.5 μg/kg_bw/d verifying the modelled data. Consequently, the exposure to pyrene is reflected by the biomonitored levels of 1-OH-Pyrene. To assess the risk for the several available European studies, the pyrene intake was used to estimate the intake of a congeners of four PAHs (PAH4: Benzo[a]anthracene – B[a]A, Benzo[b]fluorene – B[b]F, Benzo[a]pyrene – B[a]P, Chrysene – CHR) in order to calculate ELCR using the dose -response relationship. The results were in the range of 10^-7 to 10^-4 with a minimum, mean and maximum values of 1.7E-07, 1.34E-05 and 2.3E-04 respectively. For the general population the mean ELCR found to 3.12E-05 while for the occupational the ELCR value was two times higher (7.1E-05) verifying that the exposure and consequently the risk is higher in occupational setting. In addition, the group of smokers (ELCR=8.2E-05) presented larger values with respect to the group of non-smokers (ELCR=3.6E-05) corroborating the fact that smoking is a major pathway of exposure.

Exposure reconstruction assessment offers unique opportunities regarding the interpretation of HBM data, quantitatively associating them with exposure pathways contribution in the overall intake. In order to carry out exposure reconstruction, a minimum of information regarding the toxicokinetic behavior of the compound of interest is required. This allows the translation of the biomarker levels measured at a given point in time, to long-term daily intake patterns. Thus, the level of confidence regarding the intake estimates or the exposure levels of a specific pathway and route requires more detailed information regarding the daily activity pattern and microenvironments encountered, dietary habits and consumer products use. This in turn requires the use of individual HBM data, accompanied by ancillary information that would shed light on the mechanistic link between exposure dynamics and observed HBM data.