Amelia Lorenzo

Nail polish as a source of exposure to triphenyl phosphate

Triphenyl phosphate (TPHP) is primarily used as either a flame retardant or plasticizer, and is listed as an ingredient in nail polishes. However, the concentration of TPHP in nail polish and the extent of human exposure following applications have not been previously studied. We measured TPHP in ten different nail polish samples purchased from department stores and pharmacies in 2013-2014. Concentrations up to 1.68% TPHP by weight were detected in eight samples, including two that did not list TPHP as an ingredient. Two cohorts (n=26 participants) were recruited to assess fingernail painting as a pathway of TPHP exposure. Participants provided urine samples before and after applying one brand of polish containing 0.97% TPHP by weight. Diphenyl phosphate (DPHP), a TPHP metabolite, was then measured in urine samples (n=411) and found to increase nearly seven-fold 10-14h after fingernail painting (p<0.001). To determine relative contributions of inhalation and dermal exposure, ten participants also painted their nails and painted synthetic nails adhered to gloves on two separate occasions, and collected urine for 24h following applications. Urinary DPHP was significantly diminished when wearing gloves, suggesting that the primary exposure route is dermal. Our results indicate that nail polish may be a significant source of short-term TPHP exposure and a source of chronic exposure for frequent users or those occupationally exposed.

Regional comparison of organophosphate flame retardant (PFR) urinary metabolites and tetrabromobenzoic acid (TBBA) in mother-toddler pairs from California and New Jersey

The use of alternative chemical flame retardants in consumer products is increasing as the result of the phase-out of polybrominated diphenyl ethers. Today, the most commonly detected alternatives in residential furniture include the organophosphate flame retardants (PFRs) and the Firemaster (R) 550 mixture (FM550). Urinary levels of dialkyl and diaryl phosphate esters, and 2-ethylhexyl tetrabromobenzoate (EH-TBB) have been used as biomarkers of human exposure to PFRs and FM550, respectively. In a previous study, we demonstrated that toddlers had significantly higher levels of PFRs relative to their mothers in a cohort from New Jersey; however, it is unclear if there are regional differences in exposure. It is possible that exposure to PFRs may be higher in California relative to other US States due to the California flammability standard, as was seen previously observed for PBDEs. In the current study, we examined urinary levels of PFR metabolites and TBBA in 28 mother-child pairs from California, USA, collected in 2015, and compared them with levels measured in our previous study from New Jersey. Urine samples were extracted using solid-phase extraction and analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Diphenyl phosphate (DPHP), isopropyl-phenyl phenyl phosphate (ip-PPP), bis(1,3-dichloro-2propyl) phosphate (BDCIPP) and BCIPHIPP conjugates were detected in 100% of mother and child urine samples, while bis(1-chloro-2-propyl) phosphate (BCIPP), tert-butyl-phenyl phenyl phosphate (tb-PPP) and TBBA were detected in < 50% of samples. Interestingly, BCIPHIPP conjugates were detected in 100% of the urine samples, suggesting ubiquitous exposure to the parent compound, tris(1-chloro-2-propyl) phosphate (TCIPP). The current study found significantly higher BDCIPP levels in California toddlers and higher and ip-PPP levels in mothers as compared to the New Jersey cohort, which may be reflective of Californias furniture flammability standard. For example, BDCIPP levels in California children were 2.4 times higher than those in New Jersey children. Consistent with our previous work, the current study showed higher PFR and EH-TBB exposure in children, likely due to increased hand-mouth behavior. Childrens DPHP and BDCIPP levels, on average, were 5.9 times and 15 times those of their mothers. Positive correlations between paired mothers and their children were shown for DPHP and BCIPHIPP conjugates but not BDCIPP or ip-PPP. In the children, several predictors of hand-mouth behavior were associated with BDCIPP, DPHP and ip-PPP urine levels, but no associations were observed with BCIPHIPP conjugates.

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.

Predictors of urinary flame retardant concentration among pregnant women

BACKGROUND 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. METHODS Pregnant North Carolina women (n=349) provided information on their individual characteristics (e.g. age and body mass index (BMI)) as a part of the Pregnancy Infection and Nutrition Study (2002-2005). Women also provided second trimester urine samples in which six PFR metabolites were measured using mass spectrometry methods. RESULTS PFR metabolites were detected in every urine sample, with BDCIPP, DHPH, ip-PPP and BCIPHIPP detected in >80% of samples. Geometric mean concentrations were higher than what has been reported previously for similarly-timed cohorts. Women with higher pre-pregnancy BMI tended to have higher levels of urinary metabolites. For example, those classified as obese at the start of pregnancy had ip-PPP levels that were 1.52 times as high as normal weight range women (95% confidence interval: 1.23, 1.89). Women without previous children also tended to have higher urinary levels of DPHP, but lower levels of ip-PPP. In addition, we saw strong evidence of seasonal trends in metabolite concentrations (e.g. higher DPHP, BDCIPP, and BCIPHIPP in summer, and evidence of increasing ip-PPP between 2002 and 2005). CONCLUSIONS Our results indicate ubiquitous exposure to PFRs among NC women in the early 2000s. Additionally, our work suggests that individual characteristics are related to exposure and that temporal variation, both seasonal and annual, may exist.

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.

Characterizing Flame Retardant Applications and Potential Human Exposure in Backpacking Tents.

Flame retardant (FR) chemicals are applied to products to meet flammability standards; however, exposure to some additive FRs has been shown to be associated with adverse health effects. Previous research on FR exposure has primarily focused on chemicals applied to furniture and electronics; however, camping tents sold in the United States, which often meet flammability standard CPAI-84, remain largely unstudied in regards to their chemical treatments. In this study, FRs from five brands of CPAI-84-compliant, two-person backpacking tents were measured and potential exposure was assessed. Dermal and inhalation exposure levels were assessed by collecting hand wipes from 20 volunteers before and after tent setup and by using active air samplers placed inside assembled tents, respectively. Organophosphate flame retardants (OPFRs) were the most commonly detected FR in the tent materials and included triphenyl phosphate (TPHP), tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) and tris(2-chloroethyl)phosphate (TCEP). Levels of OPFRS measured on hand wipes were significantly higher post-tent setup compared to pre setup, and in the case of TDCIPP, levels were 29 times higher post setup. OPFRs were also detected at measurable concentrations in the air inside of treated tents. Significant, positive correlations were found between FR levels in treated textiles and measures of dermal and inhalation exposure. These results demonstrate that dermal exposure to FRs occurs from handling camping tents and that inhalation exposure will likely occur while inside a tent.

Prenatal exposure to organophosphates and associations with birthweight and gestational length

Organophosphate esters (OPEs) are often used as flame retardants and plasticizers. Animal data suggest exposure to OPEs could impact childrens growth and development, yet impacts on human birth outcomes are understudied. We evaluate impacts of OPE exposure on the timing of delivery and infants birthweight in the Pregnancy Infection and Nutrition Study (PIN). North Carolina women enrolled in PIN in early pregnancy and participated in follow-up through delivery. Analyses were limited to mothers recruited from 2002 to 2005, whose children participated in additional follow-up in early childhood (n = 349). Mothers collected urine samples in which OPE metabolites were assessed and birth outcomes were abstracted from medical records. Bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), isopropyl-phenyl phenyl phosphate (ip-PPP), bis(1-chloro-2-propyl) 1-hydroxy-2-propyl phosphate (BCIPHIPP) were detected in >80% of samples. Average birthweight and gestational age were 3326 g and 39.1 weeks, respectively. As data suggest that the mechanisms of action by which OPEs impact birth outcomes may be fetal sex dependent, we conducted sex-stratified statistical analyses. Women with the highest ip-PPP concentrations delivered girls 1 week earlier than women with lower levels (95% Confidence Interval (CI): -1.85, -0.15). Women with BDCIPP levels above the median had 3.99 (95% CI: 1.08, 14.78) times the odds of delivering their daughters preterm. Similarly, higher ip-PPP levels were associated with lower birthweight, but not after standardizing for gestational age. Among males, maternal ip-PPP was associated with decreased odds of preterm birth (OR = 0.21, 95% CI: 0.06, 0.68). DPHP and BCIPHIPP levels were not associated with outcomes in either sex. Results indicate that prenatal OPE exposure may impact timing of birth, though results are imprecise. Given widespread OPE exposure and the urgent need to identify and mitigate causes of preterm birth, further investigation is warranted.

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.

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.