(529b) Exposome Analysis of Polyaromatic Hydrocarbons

This study demonstrates the use of the INTEGRA platform (coupling multi-source multi-route external exposure modeling with a generic PBTK for internal exposure modeling) for estimating exposure to PAHs under a variety of scenarios of key relevance to REACH and the petroleum industry. The objective of the INTEGRA project is to bring together all information necessary for assessing the source-to-dose continuum over the entire life cycle of substances covering an extensive chemical space through the use of QSARs. The major outcome of INTEGRA is a comprehensive computational platform that integrates multimedia environmental and micro-environmental fate, exposure and internal dose within a dynamic framework in time. The platform allows multimedia interactions across different spatial scales, taking into account environmental releases and related processes at global, regional and local scale, up to the level of personal microenvironment. Coupling seamlessly exposure models with refined computational tools for internal dosimetry transforms risk assessment of environmental chemicals since it allows risk characterization to be based on internal dosimetry metrics. In this way high throughput system data such as the ones generated by Tox21 in vitro testing can be used. This opens the way towards a higher level of assessment that incorporates refined exposure (tissue dosimetry) and toxicity testing (Biological Pathway Altering Dose â?? BPAD) associated to environmental contamination at different scales.

Exposure to PAHs has became of particular scientific and regulatory interest the last year, especially in view of the potential for petroleum substances to be included in the different REACH processes (notably Evaluation and Authorisation). In order to meet the requirements of REACH, it is of particular importance the capability of models to predict direct (arising from the use of substances) and indirect (e.g. fuel combustion) PAH exposures. INTEGRA fulfils the requirements for carrying out such a comprehensive assessment and goes event beyond, allowing the estimation of internal dose, as well as the assimilation of biomonitoring data. Several scenarios were requested to be evaluated, and the scenarios with the ir results are listed below:

1] Assessing of internal exposure to PAHs (i.e. arising from all sources a consumer is exposed to: environment, food, consumer products) and the relative contribution from different routes (oral-diet; oral-dust, inhalation, dermal). For this scenario, Ï?tarting from annual emissions of 400 tones B[a]P in air within EU, and for regional emissions of 15 tones, distribution across different media and contribution of different pathways and routes was estimated. Higher intake estimates for children result from the higher bodyweight normalized inhalation rate, amount of soil and dust daily ingested; this is illustrated also in the analysis of various pathways contributions as well as when integrating among routes. Soil and dust ingestion are the dominant exposure pathways for children (uptake rate of 8.5E-03 ng/kg bw/day, followed by diet (uptake rate for both adults and children at 6-7E-04 ng/kg bw/day) and inhalation (uptake rate at 5.7-9.6E-07 ng/kg bw/day). Oral is the dominant route of exposure (uptake rate at 3.2E-03-15.2E-03 ng/kg bw/day) followed by inhalation (uptake rate at 1E-06 ng/kg bw/day) and dermal exposure (uptake rate at 9E-08 ng/kg bw/day). Mean B[a]P blood levels are up to 0.00012 ng/L for adults and 0.0007 for children, while the respective urinary concentration of the major specific metabolite 3-OH-B[a]P is 0.01 ng/L

Internal exposure to PAHs arising from specific use(s)/source(s) was also calculated and split up according to uses and sources. More specifically:

2] Assessment of specific sources such as smoked fish; when accounting for the annual emissions described above, concentration in fish was estimated by the multimedia model equal to 10^-7 μg/kg. This concentration is compared to the ones identified in the literature from smoked fish analysis, where B[a]P levels in smoked fish range from 0.08 to 4.1 μg/kg (median of 1μg/kg and consumption of 110 grams of fish). Based on the above, intake due to smoked fish consumption dominates among other pathways. The contribution of smoking fish to the total B[a]P content in fish, and consequently the contribution of the consumption of smoked fish to integrated B[a]P exposure (for fish consumers) is 1.4 ng/kg bw/day whereas the corresponding intake rate from soil or dust ingestion are 0.8-2.1E-03 ng/kg bw/day and from inhalation 4E-07 ng/kg bw/day. The respective internal dose of B[a]P upon smoked fish intake results to a peak of 0.4 ng/L of B[a]P in blood, that slowly decreases down to the blood concentration corresponding to the background exposure levels (0.01 ng/L) after almost 72 hours. The peak concentration of urinary 3-OH-B[a]P is 0.01 ng/L, observed after a couple of hours upon smoked fish intake.

3] The contribution of petroleum products (e.g. RAE - Residual Aromatic Extracts/ OLBO - other lubricants based oils) to integrated PAH exposure in Europe was reckoned on the basis of:

(a) contribution via release of PAHs to the environment (production and downstream use sites of a category of petroleum products) leading to indirect human exposure in the vicinity of an industrial plant of petroleum products. In this case inhalation becomes the dominant exposure pathway (uptake of 2.1E-01 ng/kg bw/day)

(b) contribution via consumer use of a category of petroleum products such as lubricants and coatings in rubber boots. Then, the specific consumer use dominates exposure (uptake rate of 6 ng/kg bw/day). In this case, dermal uptake is the dominant route of exposure followed by oral ingestion. However, due to the relatively limited and slow absorption through the skin, the respective peak of internal dose of B[a]P in blood is lower than the one in the smoked fish (0.2 ng/L of B[a]P in blood), but the overall area under the curve is similar, as a result of the slower absorbion into the systemic circulation and concequently the slower elimination.

4] Of particular interest is the estimation of external and internal exposure to PAHs from biomass burning for space heating. In a study evaluating the exposure to PAHs in two different urban locations (namely an urban background and a traffic station), it was identified that exposure to PAHs is greatly affected by biomass emissions. In practice, from the urban background site (where PM precence is dominated by biomass emissions), particles are characterized by lower mean aerodynamic diameter and higher PAH content. Accounting for the differences related to PM HRT deposition and the distribution of PAHs adsorbed on PM of various sizes, it was estimated that 2.5 times higher airborne B[a]P resulted in 6 times higher uptake of PAHs retained by the respiratory system. These findings bring us to the conclusion that PM emitted from wood burning for space heating (mostly in open fireplaces) contribute more to the population exposure to PAHs and to the associated health risk than the PM usually found in this urban environment. This finding brings additional evidence to the long-standing debate about the toxicity of PM emitted from biomass burning. Moreover, biomass burning is always accompanied by incomplete combustion which varies between the different combustion practices (temperatures, appliances and type of biomass used), favoring the formation of PAHs. PAHs, and the most carcinogenic compounds (5- and 6-ring) in particular, including BaP, are adsorbed to finer particles. In practice, this is also reflected in the internal dose as well; although ambient air concentration of B[a]P equivalent concentration was measured equal to 4.5 and 1.7 ng/m³ for the urban background and the traffic site respectively (for adults), the corresponding B[a]P equivalent levels in blood were estimated equal to 0.38 and 0.06 ng/L respectively.

5] Finally, the time-dynamic nature of the INTEGRA computational platform, allowed also to capture environmental, exposure and internal dose dynamics in high temporal resolution, quantifying the effect of real-life different exposure conditions related to daily activities such as driving, eating smoked fish or operating an open fireplace in actual uptake, internal dose and expected biomarker urinary levels. From this analysis it was indicated that internal exposure to B[a]P (and the other PAHs respectivelly) follows the extensively dynamic pattern of external, however, urinary 3-OH-B[a]P fluctuations are slower. In any case, spot samples of urinary PAHs may not be representative of the overall daily exposure, hence biomonitoerd based exposure assessment of PAHs requires multiple samples per day to be collected.