Health risk assessment of mixed contaminants: Interaction of metals on the uptake of polycyclic aromatic hydrocarbons in human liver cells

Abstract

A key area of uncertainty in human health risk assessment of chemical mixtures is the application of additivity of dose or effects, which may overestimate or underestimate the actual risk. In this PhD thesis, interaction effects among mixtures of benzo [a]pyrene (B[a]P), pyrene (Pyr), phenanthrene (Phe) and naphthalene (Nap) in the presence or absence of arsenic (As), cadmium (Cd), lead (Pb) is elucidated for bioaccessibility, uptake (surrogate bioavailability) and metabolism of PAHs in human systems using in vitro models. A simulated human digestion based on the use of an in vitro model (Unified BARGE Method) was used to quantify PAH bioaccessibility from exposure to contaminated soils, whereas a human liver hepatocellular (HepG2) cell line (surrogate liver) was used as an in vitro model to quantify uptake and metabolism of PAHs. This PhD To investigate bioaccessibility of PAHs, seven chemically-variant top soils were collected from background sites in Australia and were spiked with PAHs and aged up to 90 days.The UBM results suggest that the most significant interactions between PAHs and soil components controlling its bioaccessibility was completed by the first 7 days of ageing condition of this study. It is noted that there was a significant lower bioaccessibility of Data from pure solution study suggests that uptake of PAHs and in the presence of As, Cd, and Pb in HepG2 cells generally showed less than additive effects among binary, ternary and seven compound mixtures of B[a]P, Pyr, Phe and Nap. Notably, the % uptake of Phe in HepG2 cells was found to decrease significantly in the seven compound mixture (p < 0.05) which had As, Cd and Pb. Using UBM-extracted solutions, interaction effects on uptake of PAHs in HepG2 cells was found to be both additive and less than additive.Moreover, the % uptake data from UBM-extracted real soil samples showed a decrease in % uptake of B[a]P, Pyr, Phe and Nap by 0.7 %, 1.8 %, 0.4 % and 0.04 %, respectively when compared to their individual PAH % uptake in HepG2 cells from exposure to UBMextracted spiked soil samples.Results of bioaccessibility, uptake and metabolism of B[a]P, Pyr, Phe and Nap as individual compounds or mixtures in the presence or absence of As, Cd and Pb provide significant new understanding towards interaction effects of these compounds in the context of human health risk assessment. For assessment of soils contaminated with PAHs and metal/loids, it clarifies situations where additive effects can be expected rather than assuming additivity as a general rule in risk assessment of chemical mixtures.4