Stephanie C. Hammel

Measuring Personal Exposure to Organophosphate Flame Retardants Using Silicone Wristbands and Hand Wipes

Organophosphate flame retardants (PFRs) are widely used as replacements for polybrominated diphenyl ethers in consumer products. With high detection in indoor environments and increasing toxicological evidence suggesting a potential for adverse health effects, there is a growing need for reliable exposure metrics to examine individual exposures to PFRs. Silicone wristbands have been used as passive air samplers for quantifying exposure in the general population and occupational exposure to polycyclic aromatic hydrocarbons. Here we investigated the utility of silicone wristbands in measuring exposure and internal dose of PFRs through measurement of urinary metabolite concentrations. Wristbands were also compared to hand wipes as metrics of exposure. Participants wore wristbands for 5 consecutive days and collected first morning void urine samples on 3 alternating days. Urine samples were pooled across 3 days and analyzed for metabolites of the following PFRs: tris(1,3-dichloroisopropyl) phosphate (TDCIPP), tris(1-chloro-2-isopropyl) phosphate (TCIPP), triphenyl phosphate (TPHP), and monosubstituted isopropylated triaryl phosphate (mono-ITP). All four PFRs and their urinary metabolites were ubiquitously detected. Correlations between TDCIPP and TCIPP and their corresponding urinary metabolites were highly significant on the wristbands (rs = 0.5-0.65, p < 0.001), which suggest that wristbands can serve as strong predictors of cumulative, 5-day exposure and may be an improved metric compared to hand wipes.

Temporal Trends in Exposure to Organophosphate Flame Retardants in the United States

During the past decade, use of organophosphate compounds as flame retardants and plasticizers has increased. Numerous studies investigating biomarkers (i.e., urinary metabolites) demonstrate ubiquitous human exposure and suggest that human exposure may be increasing. To formally assess temporal trends, we combined data from 14 U.S. epidemiologic studies for which our laboratory group previously assessed exposure to two commonly used organophosphate compounds, tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP). Using individual-level data and samples collected between 2002 and 2015, we assessed temporal and seasonal trends in urinary bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and diphenyl phosphate (DPHP), the metabolites of TDCIPP and TPHP, respectively. Data suggest that BDCIPP concentrations have increased dramatically since 2002. Samples collected in 2014 and 2015 had BDCIPP concentrations that were more than 15 times higher than those collected in 2002 and 2003 (10β = 16.5; 95% confidence interval from 9.64 to 28.3). Our results also demonstrate significant increases in DPHP levels; however, increases were much smaller than for BDCIPP. Additionally, results suggest that exposure varies seasonally, with significantly higher levels of exposure in summer for both TDCIPP and TPHP. Given these increases, more research is needed to determine whether the levels of exposure experienced by the general population are related to adverse health outcomes.

Potential human exposure to halogenated flame-retardants in elevated surface dust and floor dust in an academic environment

ABSTRACT Most households and workplaces all over the world possess furnishings and electronics, all of which contain potentially toxic flame retardant chemicals to prevent fire hazards. Indoor dust is a recognized repository of these types of chemicals including polybrominated diphenyl ethers (PBDEs) and non‐polybrominated diphenyl ethers (non‐PBDEs). However, no previous U.S. studies have differentiated concentrations from elevated surface dust (ESD) and floor dust (FD) within and across microenvironments. We address this information gap by measuring twenty‐two flame‐retardant chemicals in dust on elevated surfaces (ESD; n=10) and floors (FD; n=10) from rooms on a California campus that contain various concentrations of electronic products. We hypothesized a difference in chemical concentrations in ESD and FD. Secondarily, we examined whether or not this difference persisted: (a) across the studied microenvironments and (b) in rooms with various concentrations of electronics. A Wilcoxon signed‐rank test demonstrated that the ESD was statistically significantly higher than FD for BDE‐47 (p=0.01), BDE‐99 (p=0.01), BDE‐100 (p=0.01), BDE‐153 (p=0.02), BDE‐154 (p=0.02), and 3 non‐PBDEs including EH‐TBB (p=0.02), BEH‐TEBP (p=0.05), and TDCIPP (p=0.03). These results suggest different levels and kinds of exposures to flame‐retardant chemicals for individuals spending time in the sampled locations depending on the position of accumulated dust. Therefore, further research is needed to estimate human exposure to flame retardant chemicals based on how much time and where in the room individuals spend their time. Such sub‐location estimates will likely differ from assessments that assume continuous unidimensional exposure, with implications for improved understanding of potential health impacts of flame retardant chemicals. HighlightsBrominated flame retardants used in electronic products accumulate in room dustVarious chemical moieties of flame retardants leach differently into room dustFlame retardant concentrations in dust differ in elevated surfaces compared to floors

Associations between flame retardant applications in furniture foam, house dust levels, and residents' serum levels

Polyurethane foam (PUF) in upholstered furniture frequently is treated with flame retardant chemicals (FRs) to reduce its flammability and adhere to rigorous flammability standards. For decades, a commercial mixture of polybrominated diphenyl ethers (PBDEs) called PentaBDE was commonly applied to foam to fulfill these regulations; however, concerns over toxicity, bioaccumulation, and persistence led to a global phase-out in the mid-2000s. Although PentaBDE is still detected in older furniture, other FR compounds such as tris(1,3-dichloroisopropyl) phosphate (TDCIPP) and Firemaster® 550 (FM550) have been increasingly used as replacements. While biomonitoring studies suggest exposure is widespread, the primary sources of exposure are not clearly known. Here, we investigated the relationships between specific FR applications in furniture foam and human exposure. Paired samples of furniture foam, house dust and serum samples were collected from a cohort in North Carolina, USA and analyzed for FRs typically used in PUF. In general, the presence of a specific FR in the sofa of a home was associated with an increase in the concentration of that FR in house dust. For example, the presence of PentaBDE in sofas was associated with significantly higher levels of BDE-47, a major component of PentaBDE, in house dust (10β=6.4, p<0.001). A similar association was observed with a component of FM550, 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB), with levels that were approximately 3 times higher in house dust when FM550 was identified in the sofa foam (p<0.01). These relationships were modified by dust loading rates in the living room and the ratio of sofa size to room size. Interestingly, levels of TDCIPP and tris(1-chloro-2-isopropyl) phosphate (TCIPP) were also higher in dust with detections in sofa foam; however, these associations were not statistically significant and may suggest there are other prominent sources of these compounds in the home. In addition, the presence of PentaBDE in sofa foam was associated with significantly higher levels of BDE-47 in serum (p<0.01). These results suggest that FR applications in sofas are likely major sources of exposure to these compounds in the home.

Characterization of Individual Isopropylated and tert-Butylated Triarylphosphate (ITP and TBPP) Isomers in Several Commercial Flame Retardant Mixtures and House Dust Standard Reference Material SRM 2585

Since the phase-out of pentaBDE in the early 2000s, replacement flame-retardant mixtures including Firemaster 550 (FM 550), Firemaster 600 (FM 600), and organophosphate aryl ester technical mixtures have been increasingly used to treat polyurethane foam in residential upholstered furniture. These mixtures contain isomers of isopropylated and tert-butylated triarylphosphate esters (ITPs and TBPPs), which have similar or greater neuro- and developmental toxicity compared to BDE 47 in high-throughput assays. Additionally, human exposure to ITPs and TBPPs has been demonstrated to be widespread in several recent studies; however, the relative composition of these mixtures has remained largely uncharacterized. Using available authentic standards, the present study quantified the contribution of individual ITP and TBPP isomers in four commercial flame retardant mixtures: FM 550, FM 600, an ITP mixture, and a TBPP mixture. Findings suggest similarities between FM 550 and the ITP mixture, with 2-isopropylphenyl diphenyl phosphate (2IPPDPP), 2,4-diisopropylphenyl diphenyl phosphate (24DIPPDPP), and bis(2-isopropylphenyl) phenyl phosphate (B2IPPPP) being the most prevalent ITP isomers in both mixtures. FM 600 differed from FM 550 in that it contained TBPP isomers instead of ITP isomers. These analytes were also detected and quantified in a house dust standard reference material, SRM 2585, demonstrating their environmental relevance.

Children's residential exposure to organophosphate ester flame retardants and plasticizers: Investigating exposure pathways in the TESIE study

BACKGROUND Following the phase-out of polybrominated diphenyl ethers (PBDEs), organophosphate esters (OPEs) have been increasingly used in consumer products and building materials for their flame retardant and plasticizing properties. As a result, human exposure to these chemicals is widespread as evidenced by common detection of their metabolites in urine. However, little is known about the major exposure pathways, or factors that influence childrens exposure to OPEs. Furthermore, little data is available on exposure to the novel aryl OPEs. OBJECTIVES To examine predictors of childrens internal exposure, we assessed relationships between OPEs in house dust and on hand wipes and levels of their corresponding metabolites in paired urine samples (n = 181). We also examined associations between urinary metabolites and potential covariates, including childs age and sex, mothers educational attainment and race, and average outdoor air temperature. METHODS Children aged 3 to 6 years provided urine and hand wipe samples. Mothers or legal guardians completed questionnaires, and a house dust sample was taken from the main living area during home visits. Alkyl chlorinated and aryl OPEs were measured in dust and hand wipes, and composite urine samples were analyzed for several metabolites. RESULTS Tris(2-chloroethyl) phosphate (TCEP), tris(2-chloroisopropyl) phosphate (TCIPP), tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), 2-ethylhexyl diphenyl phosphate (EHDPHP), triphenyl phosphate (TPHP), and 2-isopropylphenyl diphenyl phosphate (2IPPDPP) were detected frequently in hand wipes and dust (>80%), indicating that these compounds were near-ubiquitous in indoor environments. Additionally, bis(1-chloro-2-propyl) 1-hydroxy-2-propyl phosphate (BCIPHIPP), bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), mono-isopropyl phenyl phenyl phosphate (ip-PPP), and mono-tert-butyl phenyl phenyl phosphate (tb-PPP) were detected in >94% of tested urine samples, signifying that TESIE participants were widely exposed to OPEs. Contrary to PBDEs, house dust OPE concentrations were generally not correlated with urinary OPE metabolite levels; however, hand wipe levels of OPEs were associated with internal dose. For example, children with the highest mass of TDCIPP on hand wipes had BDCIPP levels that were 2.73 times those of participants with the lowest levels (95% CI: 1.67, 4.48, p < 0.0001). Of the variables examined, hand wipe level was the most consistent and strongest predictor of OPE urinary metabolite concentrations. Outdoor air temperature was also a significant predictor of urinary BDCIPP concentrations, with a 1 °C increase in temperature corresponding to a 4% increase in urinary BDCIPP (p < 0.0001). CONCLUSIONS OPE exposures are highly prevalent, and data provided herein further substantiate hand-to-mouth contact and dermal absorption as important pathways of OPE exposure, especially for young children.

Correction to Measuring Personal Exposure to Organophosphate Flame Retardants using Silicone Wristbands and Hand Wipes.

Environ. Sci. Technol. 2016, 50 (8), 4483−4491; DOI:10.1021/acs.est.6b00030 The urine concentrations reported in the original paper were raw values but mistakenly reported as specific gravity-corrected. These do not change the overall results of the paper as the associations among specific gravity-corrected urine concentrations are very similar to those among the raw values. Page 4486, Section, Statistical Analysis. The last sentence should read, “Analysis results using each set of urine concentrations were essentially not differentiable, and the associations and graphs with raw urine concentrations are presented here.” Page 4487, Section, Specific-Gravity Corrected Urine. This section heading should be labeled, “Urine.” Page 4487, Table 2. The values in this table are correct; however, the section heading under “matrix and compound” should be “Raw Urine” rather than “SG-Corrected Urine.” Page 4488, Table 3 caption. The values in this table are correct, but the caption should read “Spearman Correlation Coefficients for PFR and PFR Metabolite Levels Measured in Paired Wristbands (n = 40), Hand Wipes (n = 38), and Urine (n = 40).” Page 4488, Figure 2. The values within this figure are correct, but the headings should exclude “sg” prior to BDCIPP and BCIPHIPP. Page 4488, Section, Comparing Wristbands and Hand Wipes to Urine. In the first paragraph, it should read, “TPHP and mono-ITP concentrations on the wristbands were not correlated with DPHP, but TPHP concentrations on the wristbands were correlated to specific-gravity-corrected DPHP concentrations.” Page 4489, Table 4 caption and headings. Again, the values in this table are correct for the raw urine concentrations. Therefore, the caption should read, “Results of Regression Analyses for Associations with Raw Urinary Metabolites Based on Parent Compounds on Wristbands and Hand Wipes Categorized as Tertiles.” The headings within the table should exclude “SG-corrected” before each of the PFR metabolitesBDCIPP, BCIPHIPP, and DPHP. Page 4489, Table 5 headings. The regression analyses utilized raw urine concentrations as the outcome; therefore, the headings should exclude “SG-corrected” before each of the metabolites.

Translating the Materials Genome Into Safer Consumer Products

Viewpoint pubs.acs.org/est Translating the Materials Genome Into Safer Consumer Products Oladele A. Ogunseitan, †,‡, * Jaime M. Allgood, †,‡ Stephanie C. Hammel, † and Julie M. Schoenung § Department of Population Health & Disease Prevention, Program in Public University of California, Irvine, California 92697-3957, United States School of Social Ecology, University of California, Irvine, California 92697, United States Department of Chemical Engineering & Materials Science, University of California, Davis, California 95616, United States perspective is missing in its research foci: sustainable materials intended for use in mass-marketed products must not threaten environmental quality and human health through their production, use or disposal. It is impossible to ignore the environmental pollution legacy of new materials that have revolutionized societal needs, including the accumulation of toxic waste from electronics products and plastics, which with and without phthalates, bisphenol A, or brominated flame-retardants, represented a remarkable commercial application of materials science and manufacturing, but now threaten to be the most highly contested products in legislation and environmental protection. Traditionally, the cost-benefit trade-offs inherent in selecting materials have not been transparent, leading to regrettable outcomes and policy reversals. This is because of incompatible metrics and weights that apply to different priorities such as energy conservation, economics, disease burden, and wildlife protection. To some extent, life cycle assessments (LCAs) can address trade-offs, but there are serious gaps in databases on which LCAs rely. For example, the poster on MGI features a fluorescent light bulb presumably to represent innovation in advanced materials for energy conservation. However, recent ive years after legislation to establish the Green Chemistry studies suggest that without developing appropriate waste Initiative (GCI), the landmark California Safer Consumer management methods for bulbs, the savings in energy may not Products Law became effective on October 1st, 2013. We justify their potential detrimental impacts. 4 argue here that the development of new regulatory policies to The existing federal law to reduce exposure to chemicals used stimulate the convergence of materials development research in commerce, the 1976 Toxic Substances Control Act, is widely and public health and environmental impact assessments considered a failure. Since its implementation, the U.S. EPA has provides evidence that these topics have traditionally addressed restricted only five chemicals. Recent efforts in the U.S. separate audiences, developed different values and measure- congress to reconfigure ToSCA have stalled through opposition ment systems, and focused on incompatible goals. The United from the chemical industry. These efforts include the “Safe State’s Materials Genome Initiative (MGI) provides an Chemicals Act of 2013” introduced in April 2013 by Senators opportunity to use lessons learned from the California Frank Lautenberg (D-NJ) and Kirsten Gillibrand (D-NY) that experience to reduce the temporal and scientific gaps that would require “safe-before-sell” evidence from manufacturers challenge initiatives to prevent disease and environmental and a version introduced on May 22, 2013 as the “Chemical pollution resulting from toxic chemicals in consumer products. Safety Improvement Act of 2013” by Senators Lautenberg and The MGI aims to more rapidly meet societal needs in clean David Viter (R-LA) to gain bipartisan support. 5 energy, national security, and human welfare by developing The acceleration of materials discovery under MGI should be materials that are “at the heart of innovation, economic accompanied by increased support for other research disciplines opportunities, and global competitiveness”. 2 The MGI calls for that curb human and environmental exposures to dangerous accelerating the pace of research in computational and chemicals will lead to costly and/or regrettable applications. experimental tools, collaborative networks, and digital data The MGI “challenges researchers, policy makers, and business processingall represent a boost for the fledgling discipline of leaders to reduce the time and resources needed to bring new materials informatics. Two years after MGI started, the National Institute of Standards and Technology, DoE, and the White House’s Office of Science called the first “Materials Received: September 13, 2013 Revised: October 6, 2013 Genome Initiative Grand Challenges Summit” (June 25−26, Accepted: October 11, 2013 2013). The agenda focused on five traditional materials science Published: October 30, 2013 themes. 3 The articulated MGI goals are laudable, but a crucial F

Evaluating the Use of Silicone Wristbands to Measure Personal Exposure to Brominated Flame Retardants

Biomarkers remain the gold standard for assessing chemical exposure. However, silicone wristbands may provide some added benefits for characterizing personal exposures compared to single biomarker measurements, such as decreased costs, noninvasive sampling, and increased ease of analysis. Previously, we validated their use in characterizing exposure to organophosphate flame retardants (PFRs). However, it is unclear whether these results would extend to chemicals like polybrominated diphenyl ethers (PBDEs), which biomagnify and have longer half-lives than PFRs in the body. This study sought to determine if accumulation of PBDEs on wristbands was correlated to serum biomarkers. Adult participants ( n = 30) provided serum samples and wore wristbands for 7 days. PBDEs and 6 novel brominated flame retardants (BFRs) were measured on wristbands, and serum samples were analyzed for PBDE biomarkers. Like most PBDE congeners, 5 of 6 novel BFRs were frequently detected on wristbands (≥90% of bands). In particular, decabromodiphenyl ethane (DBDPE) was detected in all wristbands in this study and was significantly correlated with BDE-209, suggesting a similar source and exposure pathway. Wristband levels of BDE-47, -99, -100, and -153 were significantly and positively associated with respective serum biomarkers ( rs = 0.39-0.57, p < 0.05). This study demonstrates that silicone wristbands can accurately detect personal PBDE exposures.

Biomarkers of exposure to SVOCs in children and their demographic associations: The TESIE Study

Semi-volatile organic compounds (SVOCs) are used extensively in consumer and personal care products; electronics; furniture; and building materials and are detected in most indoor environments. As a result, human exposure to mixtures of SVOCs is wide-spread. However, very few studies have measured biomarkers of exposure to multiple SVOC classes, and exposure determinants have not been thoroughly explored, particularly for young children. In this study, we investigated biomarkers of exposure to SVOCs among children (age 3-6 years), who may experience higher exposures and be more susceptible to adverse health outcomes than other age groups. We enrolled 203 participants in the Toddlers Exposure to SVOCs in Indoor Environments (TESIE) study (181 provided urine samples and 90 provided serum samples).We quantified 44 biomarkers of exposure to phthalates, organophosphate esters (OPEs), parabens, phenols, antibacterial agents and per- and polyfluoroalkyl substances (PFASs); we detected 29 of the 44 biomarkers in >95% of samples, and many biomarkers were detected at higher median concentrations than those previously reported in the U.S. general population. Demographic characteristics were associated with differences in concentrations. In general, non-Hispanic white race and higher maternal education were associated with lower concentrations, even after adjusting for other potential confounding variables. Our results suggest that outdoor temperature at the time of biospecimen collection may be a particularly important and under-evaluated predictor of biomarker concentrations; statistically significant relationships were observed between 10 biomarkers and outdoor temperature at the time of collection. A complex correlation structure was also observed among the biomarkers assessed. By and large, statistically significant correlations between biomarkers of exposure to phthalates, parabens, phenols, and OPEs were positive. Conversely, although PFASs were positively correlated with one another, they tended to be negatively correlated with other biomarkers where significant associations were observed. Taken together, our results provide evidence that the assessments of SVOC-associated health impacts should focus on chemical mixtures.