Bioavailability of HBCD/TBB/TBPH from dust and oil vehicles in Sprague-Dawley rats

Authors: Hakk, Heldur; Lupton, Sara; Singh, Anuradha

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 7/7/2017
Publication Date: 8/20/2017
Citation: Hakk, H., Lupton, S.J., Singh, A. 2017. Bioavailability of HBCD/TBB/TBPH from dust and oil vehicles in Sprague-Dawley rats [abstract]. Dioxin 2017. August 20-25, 2017. Vancouver, Canada. Paper No. 10025.

Interpretive Summary: .

Technical Abstract: Hexabromocyclododecane (HBCD), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB), and bis(2-ethylhexyl)-3,4,5,6-tetrabromophtalate (TBPH) are brominated flame retardants (BFR) and are considered POPs because they persist in the environment, bioaccumulate in tissues, are toxic, and can be transported long distances. Air transport has been demonstrated for HBCDs and TBB/TBPH [1]. In terms of human exposures, the major routes for HBCDs and TBB/TBPH are homes, offices, and car environments due to the presence of dust [2]. HBCD and TBB/TBPH have been identified in household dust at concentrations exceeding 1 µg/g, and their dust levels have been correlated to human plasma levels [3]. It is believed that dust may be the most important route for HBCD and TBB/TBPH exposure in young children and that adults may be equally exposed to these BFRs through diet and indoor dust. A study was initiated to demonstrate the mammalian bioavailability of these three BFRs at environmentally-relevant levels when bound to household dust, and compare these results to the bioavailability from an oil vehicle in male rats. Standard reference material (SRM) 2585, a well-characterized household dust, was extracted by a published method [4] quantitated by liquid chromatography-mass spectrometry (LC-MS) for a-, b-, and g-HBCD isomers (ratio of 7:5:88 of a-, b-, and g-HBCD). An oil vehicle was prepared whose daily administration duplicated the natural HBCD/TBB/TBPH exposure from 390 mg of dust/d (7.4, 1.6, 46.4, 15.6, and 254.3 ng of a-, b-, g-HBCD, TBB, and TBPH, respectively). Male Sprague-Dawley rats (n=20; 220-235g) were randomly divided into a Control group (n=3), an Oil-dosed group (n=13), and a Dust-dosed group (n=4). The Oil group was further divided into a 3 d exposure (n=3), a 7 d exposure (n=3), a 14 d exposure (n=3), and a 21 d exposure (n=4) to determine steady state conditions. Feces and urine were collected daily throughout the study. Twenty four hours after their last exposure, the rats were sacrificed and adipose tissue, brain, GI tract, kidney, liver, lung, muscle, blood, and skin were collected. Currently, blood, adipose tissue and liver have been extracted by published methods [5] and the levels of HBCD isomers were determined by LC-MS, while the levels of TBB and TBPH will be determined by GC-MS. HBCD isomers were detected in blood, adipose, and liver of both dose groups, suggesting these BFRs are bioavailable from both oil vehicle and dust vehicle, although the extent of bioavailability is still being determined. The b-HBCD isomer was below the limit of detection in all tissues, while a-HBCD could not be detected in blood or Dust-dosed adipose tissue; it was detected in all liver samples. As was the case in the dust samples, g-HBCD was the dominant isomer (66.7-85.1%) in blood, adipose and liver samples. The concentration of g-HBCD in the administered SRM 2585 dust sample was 6.3-fold higher than a-HBCD, and the ratio declined to 2.0-3.1 in the Oil-dosed rat liver, suggesting stereoisomerization or isomer-selective metabolism. The preliminary data indicates that BFRs in household dust are bioavailable when ingested. Other tissue and excreta analyses are ongoing.