ReviewAdvances in in vitro methods to evaluate oral bioaccessibility of PAHs and PBDEs in environmental matrices
Introduction
Persistent organic pollutants (POPs), such as most polycyclic aromatic hydrocarbons (PAHs) and polybrominated diphenyl ethers (PBDEs), are characterized by low aqueous solubility, low vapor pressure, lipophilic properties and long half lives in soils (Juhasz and Naidu, 2000). Due to their adverse impacts on human health (Darnerud et al., 2001), it is important to determine their exposure to humans from different environmental matrices including soil, dust and food. Human exposure to POPs mainly occurs from three pathways including inhalation, dermal absorption and oral ingestion, with the oral ingestion pathway being the most important, which includes consumption of food and incidental ingestion of soil and dust.
Oral ingestion is a major exposure route for the most susceptible sub-group of the population, i.e., young children with high frequency of mouth-hand behavior. When quantifying exposure to ingested contaminants, 100% bioavailability is usually assumed, i.e., all ingested contaminants are soluble in gastrointestinal (GI) tract and absorbed into systemic circulation. However, there is growing evidence to indicate that total concentration may not represent the fraction of the contaminant that is absorbed into the body (i.e., the bioavailable fraction), which exerts a negative effect on human health. As a result, understanding POP bioavailability is important to accurately quantify the risk of contaminant exposure to humans (Cui et al., 2013, Rostami and Juhasz, 2011). In the context of human health, contaminant bioavailability can be described in absolute or relative terms. Absolute bioavailability (ABA) can be defined as the fraction of a dose reaching the systemic circulation (Oomen et al., 2003). Relative bioavailability (RBA) is the comparative bioavailability of different forms or exposure media containing the contaminant, which is expressed as a fractional relative absorption factor (Ruby et al., 1999). For example, Smith et al. (2012) used DDT-spiked sand as the dosing vehicle to measure the RBA of DDT in contaminated soils. It was calculated by comparing the adipose tissue concentration of DDT in soil-dosed mice to that of sand-dosed mice. Related to bioavailability is the concept of bioaccessibility, referring to the fraction of contaminant dissolved in simulated GI solution, which can be potentially taken up by intestinal cells, and can be measured by physiologically based in vitro methods.
In vivo assays are preferred methods as they can directly determine the bioavailability of POPs in different matrices. However, they are expensive and impractical for large scale testing. Simple and inexpensive in vitro methods, which simulate digestion processes in human GI tract, have been developed as surrogates to predict POP bioavailability (Dean and Ma, 2007). The underlying principle of in vitro assays is that the amounts of a contaminant that are extracted by digestive fluids are correlated to the amounts that are potentially absorbed following ingestion of a contaminated matrix. Although in vitro assays offer an attractive alternative to in vivo assays, their application to refine POP exposure is still in the developmental phase.
This paper reviews the current status of in vitro methods to predict POP bioavailability in different matrices including soil, food and indoor dust. Emphasis is placed on recent developments to overcome method limitations, including the use of a sorption sink to overcome solubility constraints associated with hydrophobic organic contaminants, and the use of epithelial Caco-2 cell lines to simulate human sorption of contaminants. While the principles described here applicable to all POPs, this review focuses primarily on two contaminant classes namely PAHs and PBDEs. These contaminants represent both traditional and emerging POPs with many compounds within each class having a range of physiochemical and toxicological properties.
Section snippets
Presence of PAHs and PBDEs in the environment
PAHs refer to hydrocarbons containing >2 fused benzene rings in different arrangements. There are several hundreds of PAHs, but only 16 PAH compounds are listed as priority contaminants by the US Environmental Protection Agency (Gan et al., 2009). PBDEs are a group of brominated compounds comprising 209 congeners, which have been used as flame retardants to reduce the flammability of furniture, textiles and electronic equipment.
Soil is the primary reservoir for PAHs compared with other matrices
In vivo bioavailability of PAHs and PBDEs
The absolute bioavailability (ABA) or relative bioavailability (RBA) of PAHs in contaminated soils has been assessed using different animal models and biological endpoints (Table 3). James et al. (2011) reported that the ABA of PAHs based on swine blood serum as the endpoint was 0.01–29% (The large range of ABA may be due to the wide PAH concentration range, i.e., 0.17–650 μg BaP equivalents g−1 soil, in the 9 soil samples). Pu et al. (2004) reported 15–49% and 23–35% in phenanthrene-spiked
In vitro bioaccessibility of PAHs and PBDEs
Several in vitro methods have been applied for bioaccessibility measurement of POPs, including the physiologically based extraction test (PBET), simulator of the human intestinal microbial ecosystem (SHIME), in vitro gastrointestinal method (IVG), Dutch National Institute for Public Health and the Environment (RIVM) method, and Fed ORganic Estimation human Simulation Test (FOREhST). In the following section, an overview of these methods is provided. In vitro methods for PAH bioaccessibility
Improvements and challenge for in vitro methods
While several in vitro methods have been adopted by different countries to predict the RBA of inorganic contaminants in soils, (e.g., As and Pb), the lack of in vivo-in vitro correlation (IVIVC) for organic contaminants limits their use to predict RBA of POPs in the environment. To improve IVIVC, several challenges are highlighted below.
Conclusions
Traditional methods for assessing POP exposure for human health risk assessment utilize total contaminant concentrations in environment matrix. This approach may overestimate the exposure, which may result in unnecessary remediation efforts. During the past two decades, in vitro methods have been developed to measure the oral bioaccessibility of POPs in soil, indoor dust, and food, and potentially predict their bioavailability in environment matrix. The applications and challenge for these
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