Metabolites of Organophosphate Flame Retardants and 2-Ethylhexyl Tetrabromobenzoate in Urine from Paired Mothers and Toddlers

Abstract

As a result of the polybrominated diphenyl ether (PBDE) ban in the mid-2000s, the chemical flame retardant market has moved toward alterative compounds including chlorinated alkyl and nonchlorinated aryl organophosphate flame retardants (OPFRs) as well as aromatic brominated compounds such as Firemaster 550 (FM550). Recent studies have shown that the OPFRs and Firemaster 550 components are frequently detected in polyurethane foams and in indoor dust. Some OPFRs are considered carcinogenic and/or neurodevelopmental toxicants, and children's exposure to these compounds is a concern. OPFRs are readily metabolized and excreted in the urine as their dialkyl and diaryl compounds which function as biomarkers for OPFR exposure. Limited research has shown that adults are broadly exposed to OPFRs, but nothing is known about children's exposure. Similarly, 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB), a FM550 component, is metabolized to tetrabromobenzoic acid (TBBA). The current study measured levels of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), bis(1-chloro-2-propyl) phosphate (BCIPP), diphenyl phosphate (DPHP), 2 alkylated DPHPs, and TBBA in urine collected in 2013 from 21 US mother-toddler pairs. BDCIPP, DPHP, and ip-DPHP were detected in 100%, 98%, and 96% of all individuals, whereas BCIPP and tert-butyl-DPHP (tb-DPHP) were only detected in 8% and 13%. Further, TBBA was detected in 27% of adults but 70% of children. Overall, children had higher urinary levels of BDCIPP, DPHP, ip-DPHP, and TBBA as compared to their mothers, suggesting higher exposure. For example, on average, BDCIPP levels in children were 4.9 times those of mothers. BDCIPP and DPHP levels in mother's urine were also significantly correlated with levels in children's urine, suggesting similar exposure routes, likely in the home environment. Various potential predictors of OPFR exposure were assessed using a questionnaire. In children some predictors of hand-mouth exposure were associated with elevated BDCIPP and DPHP levels (e.g., less frequent hand washing for BDCIPP). Overall, these trends are consistent with higher flame retardant levels in children as a result of increased hand-mouth behavior and elevated dust exposure.

Editor’s Highlight: Transplacental and Lactational Transfer of Firemaster® 550 Components in Dosed Wistar Rats

“…While measured in other biological samples (Butt et al, 2014;Hoffman et al, 2015), this was the first study to the authors' knowledge to confirm ip-PPP as a urinary metabolite of ITPs in a controlled dosing experiment. This establishes ip-PPP as a useful biomarker for exposure to ITPs in human populations.…”

“…In addition, EH-TBB and BEH-TEBP have been detected in atmospheric particles from the European Arctic and in marine mammals, underscoring the potential for long-term transport of these compounds and illustrating their current farreaching global distribution (Lam et al, 2009;Salamova et al, 2014;Zhu et al, 2014). Furthermore, EH-TBB and BEH-TEBP have been measured in human hair and nails and the urinary metabolite of EH-TBB, 2,3,4,5-tetrabromobenzoic acid (TBBA), has been frequently detected in recent analyses of human urine, suggesting that human exposure to FM 550 is widespread (Butt et al, 2014;Hoffman et al, 2014;Liu et al, 2015). Other metabolites of FM 550 measured previously in urine include diphenyl phosphate (DPHP), isopropylphenyl phenyl phosphate (ip-PPP), and mono-(2-ethylhexyl) tetrabromophthalate (TBMEHP) (Van den Eede et al, 2013bEede et al, , 2014Silva et al, 2015) (Fig.…”

“…EH-TBB, BEH-TEBP, TPHP, and ITPs were quantified using our previously published GC/MS methods (Stapleton et al, 2008(Stapleton et al, , 2009. TBBA, DPHP, and ip-PPP were quantified using previously published LC/MS/MS methods (Butt et al, 2014;Cooper et al, 2011;Roberts et al, 2012) (See Supplementary Figs. 2-4 for representative chromatograms).…”

Development and validation of a multi-residue method for the analysis of brominated and organophosphate flame retardants in indoor dust

“…Brominated flame retardants (BFRs), including polybrominated diphenyl ethers (PBDEs) have been widely used for decades. However, concerns regarding the bioaccumulation in human tissues and potential adverse health effects of PBDEs have resulted in their phase-out in some countries, leading to an increase in the production and use of alternative flame retardants, including OPFRs [2,3]. Global demand for flame retardants is projected to increase by 4.6 % per year until 2018 to reach a volume of 2.8 million tonnes [4].…”

Disposition of the Emerging Brominated Flame Retardant, 2-Ethylhexyl 2,3,4,5-Tetrabromobenzoate, in Female SD Rats and Male B6C3F1 Mice: Effects of Dose, Route, and Repeated Administration

“…Sampling found a US population had serum levels of 1.3-54 ng EH-TBB/g lipid whereas amounts in hair and nail samples from these same individuals contained 7.6-4540 and 11-1210 ng EH-TBB/g, respectively (Liu et al, 2016a). Urinary metabolites of EH-TBB were found in both adults and children, with detection frequency more than double for children (70%) relative to the paired adult (27%) (Butt et al, 2014), consistent with previous conclusions that children have more frequent and likely higher exposures to contaminants in dust (Harrad et al, 2008).…”