Urinary Metabolites of Organophosphate Flame Retardants: Temporal Variability and Correlations with House Dust Concentrations

Background: A reduction in the use of polybrominated diphenyl ethers (PBDEs) because of human health concerns may result in an increased use of and human exposure to organophosphate flame retardants (OPFRs). Human exposure and health studies of OPFRs are lacking. Objectives: We sought to define the degree of temporal variability in urinary OPFR metabolites in order to inform epidemiologic study design, and to explore a potential primary source of exposure by examining the relationship between OPFRs in house dust and their metabolites in urine. Methods: Nine repeated urine samples were collected from 7 men over the course of 3 months and analyzed for bis(1,3-dichloro-2-propyl) phosphate (BDCPP) and diphenyl phosphate (DPP), metabolites of the OPFRs tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and triphenyl phosphate (TPP), respectively. Intraclass correlation coefficients (ICCs) were calculated to characterize temporal reliability. Paired house dust and urine samples were collected from 45 men. Results: BDCPP was detected in 91% of urine samples, and DPP in 96%. Urinary BDCPP showed moderate-to-strong temporal reliability (ICC range, 0.55–0.72). ICCs for DPP were lower, but moderately reliable (range, 0.35–0.51). There was a weak [Spearman r (rS) = 0.31] but significant (p = 0.03) correlation between urinary BDCPP and TDCPP concentrations in house dust that strengthened when nondetects (rS = 0.47) were excluded. There was no correlation between uncorrected DPP and TPP measured in house dust (rS < 0.1). Conclusions: Household dust may be an important source of exposure to TDCPP but not TPP. Urinary concentrations of BDCPP and DPP were moderately to highly reliable within individuals over 3 months

Endocrine-Mediated Mechanisms of Metabolic Disruption and New Approaches to Examine the Public Health Threat

Obesity and metabolic disorders are of great societal concern and generate substantial human health care costs globally. Interventions have resulted in only minimal impacts on disrupting this worsening health trend, increasing attention on putative environmental contributors. Exposure to numerous environmental contaminants have, over decades, been demonstrated to result in increased metabolic dysfunction and/or weight gain in cell and animal models, and in some cases, even in humans. There are numerous mechanisms through which environmental contaminants may contribute to metabolic dysfunction, though certain mechanisms, such as activation of the peroxisome proliferator activated receptor gamma or the retinoid x receptor, have received considerably more attention than less-studied mechanisms such as antagonism of the thyroid receptor, androgen receptor, or mitochondrial toxicity. As such, research on putative metabolic disruptors is growing rapidly, as is our understanding of molecular mechanisms underlying these effects. Concurrent with these advances, new research has evaluated current models of adipogenesis, and new models have been proposed. Only in the last several years have studies really begun to address complex mixtures of contaminants and how these mixtures may disrupt metabolic health in environmentally relevant exposure scenarios. Several studies have begun to assess environmental mixtures from various environments and study the mechanisms underlying their putative metabolic dysfunction; these studies hold real promise in highlighting crucial mechanisms driving observed organismal effects. In addition, high-throughput toxicity databases (ToxCast, etc.) may provide future benefits in prioritizing chemicals for in vivo testing, particularly once the causative molecular mechanisms promoting dysfunction are better understood and expert critiques are used to hone the databases. In this review, we will review the available literature linking metabolic disruption to endocrine-mediated molecular mechanisms, discuss the novel application of environmental mixtures and implications for in vivo metabolic health, and discuss the putative utility of applying high-throughput toxicity databases to answering complex organismal health outcome questions

Urinary metabolites of organophosphate flame retardants and their variability in pregnant women

Organophosphate flame retardants (OPFRs) are commonly added to consumer products to reduce their flammability. Based on levels of OPFRs in indoor environments, human exposure is likely chronic and ubiquitous. Animal studies suggest that exposure to some OPFRs may result in adverse health impacts, particularly for tris (1,3-dichloropropyl) phosphate (TDCPP); however, human data on the impacts of exposure to OPFRs are lacking. To design human studies, more information is needed on the stability of measured OPFRs in human samples over time. In this study, we sought to assess the degree of temporal variability of urinary TDCPP and triphenyl phosphate (TPP) metabolites throughout pregnancy in a cohort of women from central North Carolina

Predictors of urinary flame retardant concentration among pregnant women

Organophosphate compounds are commonly used in residential furniture, electronics, and baby products as flame retardants and are also used in other consumer products as plasticizers. Although the levels of exposure biomarkers are generally higher among children and decrease with age, relatively little is known about the individual characteristics associated with higher levels of exposure. Here, we investigate urinary metabolites of several organophosphate flame retardants (PFRs) in a cohort of pregnant women to evaluate patterns of exposure

Apolipoprotein A–I binding to anionic vesicles and lipopolysaccharides: Role for lysine residues in antimicrobial properties

AbstractHuman apolipoprotein A–I (apoA–I) is a 28kDa protein and a major component of high-density lipoproteins, mediating several essential metabolic functions related to heart disease. In the present study the potential protective role against bacterial pathogens was explored. ApoA–I suppressed bacterial growth of Escherichia coli and Klebsiella pneumoniae. The protein was able to bind lipopolysaccharides and showed a strong preference for bilayer vesicles made of phosphatidylglycerol over phosphatidylcholine. Lysine side chains of apoA–I were acetylated to evaluate the importance of electrostatic forces in the binding interaction with both membrane components. Electrophoresis properties, dot blot analysis, circular dichroism, and fluorescence spectroscopy to probe for changes in protein structure indicated that the acetylated protein displayed a strongly reduced lipopolysaccharide and phosphatidylglycerol binding. A mutant containing only the N-terminal domain of apoA–I also showed a reduced ability to interact with the membrane components, although to a lesser extent. These results indicate the potential for apoA–I to function as an antimicrobial protein and exerts this function through lysine residues

Exposure to flame retardant chemicals on commercial airplanes

Background: Flame retardant chemicals are used in materials on airplanes to slow the propagation of fire. These chemicals migrate from their source products and can be found in the dust of airplanes, creating the potential for exposure. Methods: To characterize exposure to flame retardant chemicals in airplane dust, we collected dust samples from locations inside 19 commercial airplanes parked overnight at airport gates. In addition, hand-wipe samples were also collected from 9 flight attendants and 1 passenger who had just taken a cross-country (USA) flight. The samples were analyzed for a suite of flame retardant chemicals. To identify the possible sources for the brominated flame retardants, we used a portable XRF analyzer to quantify bromine concentrations in materials inside the airplanes. Results: A wide range of flame retardant compounds were detected in 100% of the dust samples collected from airplanes, including BDEs 47, 99, 153, 183 and 209, tris(1,3-dichloro-isopropyl)phosphate (TDCPP), hexabromocyclododecane (HBCD) and bis-(2-ethylhexyl)-tetrabromo-phthalate (TBPH). Airplane dust contained elevated concentrations of BDE 209 (GM: 500 ug/g; range: 2,600 ug/g) relative to other indoor environments, such as residential and commercial buildings, and the hands of participants after a cross-country flight contained elevated BDE 209 concentrations relative to the general population. TDCPP, a known carcinogen that was removed from use in children’s pajamas in the 1970’s although still used today in other consumer products, was detected on 100% of airplanes in concentrations similar to those found in residential and commercial locations. Conclusion: This study adds to the limited body of knowledge regarding exposure to flame retardants on commercial aircraft, an environment long hypothesized to be at risk for maximum exposures due to strict flame retardant standards for aircraft materials. Our findings indicate that flame retardants are widely used in many airplane components and all airplane types, as expected. Most flame retardants, including TDCPP, were detected in 100% of dust samples collected from the airplanes. The concentrations of BDE 209 were elevated by orders of magnitude relative to residential and office environments