Abstract/Summary

Polybrominated diphenyl ethers (PBDEs) are flame retardants (FRs) used as additives against fire ignition accidents, present in everyday consumer products including carpets, electronic appliances, clothing and textiles, thermal insulation and cable coatings. PBDE continuous and excessive use in consumer products, has raised concerns regarding their potential adverse health effects including endocrine and thyroid disruption and neurodevelopmental disorders in children. Hence, legislative restrictions on the production and use of PBDEs in the global market have been imposed by the competent authorities. However, limited data exist on the fate, environmental levels and potential effects on human health of PBDE alternatives such as emerging halogenated FRs (EHFRs), phthalate esters (PEs), non-halogenated phosphorous FRs (PFRs) and alternative plasticisers. Oral bioaccessibility (i.e. uptake) studies have been widely used as a research tool to determine the potential human exposure to ingested contaminants via solid matrices such as indoor dust. Colon Extended ­ Physiologically Based Extraction Test (CE-PBET) is a well-established bioaccessibility protocol specifically developed for the testing of organic compounds, rich in dietary components which act as a “biological sink” for organic pollutants, enhancing thus the sorption capacity of the system. Also, strong adsorbents such as Tenax TA®, silicone-activated contaminant traps, cyclodextrins and silicone rods have also been proposed as “absorption sink” materials. Taken all together, the aim of the PhD studies presented here is two-fold: a) to assess human exposure to legacy and alternatives FRs via indoor dust ingestion and inhalation and b) to develop a robust and unified oral bioaccessibilty method with the inclusion of Tenax TA® as a non-biologically active “infinite sink” to the previously established CE-PBET model. Regarding the in vitro gut bioaccessibility, a novel physical separation of the incubated dust with the Tenax TA was successful by employing a regenerated cellulose (RC) dialysis membrane method. The newly developed system was optimised for Tenax TA® bead loading (i.e. 0.25, 0.5 or 0.75g) and allowed sorption to be studied in the stomach, small intestine and colon compartments. Our results show that sorption on Tenax TA® in the stomach was 43.7% and 25.6% for BDE28 and BDE47 respectively, unlike in the colon compartment which was nearly 50% for BDE154 and BDE183. With Tenax TA® inclusion, gut bioaccessibility reached 40% for BDE153 and BDE183, with greater increases seen for less hydrophobic FRs such as BDE28 and BDE47 (60.6%). The combination of Tenax TA® as an infinite sink together with the lipid-rich colon compartment of CE-PBET act as a substantial advance towards a cost-effective and more realistic estimates of FR uptake via the gut and can liaise regulators to redefine human exposure estimates. We also investigated the presence of PBDEs and alternative FRs such as emerging halogenated FRs (EHFRs) and organophosphate flame retardants (PFRs) in indoor dust samples from British and Norwegian houses as well as British stores and offices. BDE209 was the most abundant PBDE congener with median concentrations of 4,700 ng g-1 and 3,400 ng g-1 in UK occupational and house dust, respectively, 30 and 20 fold higher than in Norwegian house dust. Monomeric PFRs (m-PFRs), including triphenyl phosphate (TPHP), tris(chloropropyl) phosphate (TCPP) and tris(2-chloroethyl) phosphate (TCEP) dominated all the studied environments. This is the first report of isodecyldiphenyl phosphate (iDPP) and trixylenyl phosphate (TXP) in indoor environments. iDPP was the most abundant oligomeric PFR (o-PFR) in all dust samples, with median concentrations one order of magnitude higher than TXP and bisphenol A bis(diphenyl phosphate (BDP). iDPP and TXP worst-case scenario exposures for British workers during an 8h exposure in the occupational environment were equal to 34 and 1.4 ng kg bw-1 day-1 , respectively considerably below the proposed reference values. With respect to inhalation as an alternative route of exposure, this is the first study assessing the in vitro pulmonary uptake of established PEs including dimethyl phthalate (DMP), diethyl phthalate (DEP) and di-(2-ethylhexyl) phthalate (DEHP) and alternative plasticisers used as phthalate substitutes such as bis(2-ethylhexyl) terephthalate (DEHT) and cyclohexane-1,2- dicarboxylic acid diisononyl ester (DINCH) present in indoor dust. Two artificial lung fluids, mimicking two distinctively different interstitial conditions were used, namely artificial lysosomal fluid (ALF, pH=4.5) representing the fluid that inhaled particles would contact after phagocytosis by alveolar and interstitial macrophages within the lung and Gamble’s solution (GMB, pH=7.4) as a fluid for deep lung deposition of dust within the interstitial fluid of the lung. Our results suggest that low molecular weight (MW) and short-chained phthalates such as DMP and DEP are highly bioaccessible (>75%) in both artificial pulmonary media tested, whereas high MW compounds such as DEHP, DINCH and DEHT were <5% bioaccessible. Such findings confirm the hypothesis of hydrophobicity and water solubility primarily influencing inhalation bioaccessibility of organic pollutants. Finally, human exposure to alternative FRs is expected to increase in the future, hence continuous monitoring is required. The in vitro bioaccessibility methods presented in this thesis can thus form the foundation upon which an integrated and robust testing strategy for chemicals of emerging concern can be built.