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Brominated flame retardants (BFRs) are synthetic compounds which are added to consumer and industrial products to inhibit the propagation of fire. Several of the most predominantly used BFRs have been banned or phased out of use due to their toxicity, persistence in the environment, and potential to bioaccumulate. Novel brominated flame retardants (NBFRs) are replacement compounds of legacy BFRs and are generally designed to be less bioaccumulative and persistent in the environment. The NBFRs, bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB), and 1,2,5,6-tetrabromocyclooctane (TBCO) are components of several flame retardants mixtures including Firemaster® 550 and Saytex® BC-48 and are (potential) major replacements of legacy BFRs. These compounds have been detected in the outdoor and indoor environments, in tissues of wildlife, and serum/tissues of humans, though little information exists regarding potential toxicities and concentrations of these compounds in the indoor environment. Therefore, the aim of this research was to characterize toxicities of these compounds and investigate important parameters of exposure in early childhood environments (ECEs). Preliminary characterization of toxicities of TBPH, TBB, and TBCO focused on potential endocrine disrupting effects as these compounds were structurally similar to known endocrine disrupting compounds (EDCs). The screening level investigations of toxicity employed cellular assay systems to determine binding activities with hormone receptors and modulation of production of sex steroid hormones. Results obtained with these in vitro assays demonstrated potentials of NBFRs to modulate endocrine function through interactions with estrogen and androgen receptors and via alterations to the synthesis of 17-β-estradiol and testosterone. Therefore, further characterization of endocrine disrupting effects of these NBFRs was warranted. Short-term fish fecundity assays coupled to investigations of molecular mechanisms of effect along the hypothalamus-pituitary-gonadal-liver (HPGL) axis confirmed that TBPH, TBB, and TBCO affected normal endocrine functions. Exposure to a mixture of TBPH:TBB or TBCO reduced fecundity of Japanese medaka (Oryzias latipes) and caused alterations in transcript abundances of genes across the HPGL-axis. Though no distinct mechanisms of effects were determined, a pattern of down-regulation of genes across all tissues of the HPGL-axis was observed following exposure to the mixture of TBPH:TBB, while exposure to TBCO alone elicited organ-specific and dose-dependent alterations of expression of genes involved in steroidogenesis, metabolism of cholesterol, and estrogen signaling. Concentrations of TBPH and TBB in dust from ECEs collected during summer and winter were determined to elucidate important factors of exposure of children. Novel hydroxylated isomers of TBPH and TBB were detected and characterized in dust from ECEs for the first time. Concentrations of TBPH, TBB, OH-TBPHs, and OH-TBBs in dust from ECEs from Saskatoon, SK, Canada were among the greatest reported globally though no seasonal differences in concentrations of compounds in dust were observed. Greater concentrations of these NBFRs were detected in microenvironments with greater numbers of children’s toys which indicated that concentrations in dust might be related to increases in density of these consumer products. To further characterize exposure of children to NBFRs, bioaccessibilities of TBPH, TBB, OH-TBPHs, and OH-TBBs in dust from ECEs were assessed in an in vitro incubation assay system. TBPH and OH-TBPHs were minimally bioaccessible where TBB and OH-TBBs were moderately-highly bioaccessible, which indicated that TBPH and OH-TBPHs would not likely be readily bioavailable from dust in in vivo systems. The data generated in this thesis is important to inform accurate assessments of risk of these novel brominated flame retardants.



Novel Brominated Flame Retardants, Indoor Contamination, Indoor dust, Endocrine Disruption



Doctor of Philosophy (Ph.D.)


Toxicology Centre




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