Organophosphate Ester Flame Retardants Research Articles

Micro-extraction method for the analysis of flame retardants in dust collected from air filters from HVAC systems

Dust is a sink for many semi-volatile compounds including flame retardants of the organophosphate ester (OPE) and brominated flame-retardant (BFR) classes. Given the large amount of time that we spend indoors, our exposure to these compounds via dust is of significant interest. Here, we present a novel microextraction approach to determine quantitative levels of selected OPEs and BFRs sampled from residential air filters from HVAC systems using a small volume of solvent. Dust samples (25 mg) is extracted with 1 mL of hexane/acetone (50/50, v/v). Upon solvent extraction of these HVAC dust samples, the analytes (TCPP, TDCPP, TPHP, T24DtBPP, TBBPA, and TriBBPA) were quantified via gas chromatography-mass spectrometry (GC/MS) or liquid chromatography-mass spectrometry (LC/MS). The methods for extracting these compounds from HVAC dust samples are detailed here with extensive method validation data to demonstrate accuracy and precision of these methods.•Dust is a sink for many semi-volatile compounds, including novel or emerging indoor pollutants like the organophosphate ester flame retardant T24DtBPP.•Here, a small amount of dust (25 mg) is extracted with a small volume of solvent (1 mL hexane and acetone) prior to analysis via chromatographic separation and mass spectrometric detection.

Erratum: "Associations of Organophosphate Ester Flame Retardant Exposures during Pregnancy with Gestational Duration and Fetal Growth: The Environmental influences on Child Health Outcomes (ECHO) Program".

Erratum: "Associations of Organophosphate Ester Flame Retardant Exposures during Pregnancy with Gestational Duration and Fetal Growth: The Environmental influences on Child Health Outcomes (ECHO) Program".

Organophosphate ester flame retardants and plasticizers affect the phenotype and function of HepG2 liver cells.

Exposure to the organophosphate esters (OPEs), used as flame retardants and plasticizers, is associated with a variety of adverse health effects including an increase in the incidence of non-alcoholic fatty liver disease. The goal of this study was to investigate the effects of six OPEs, all detected in Canadian house dust, on the phenotype and function of HepG2 liver cells. We used high-content imaging to investigate the effects of these OPEs on cell survival, mitochondria, oxidative stress, lipid droplets, and lysosomes. Effects on the autophagy/lipophagy pathway were evaluated using confocal microscopy. The triaryl OPEs (isopropylated triphenylphosphate [IPPP], tris(2-butoxyethyl) phosphate [TBOEP], and triphenyl phosphate [TPHP]) were more cytotoxic than non-triaryl OPEs (tris(methylphenyl) phosphate [TMPP], tris(1-chloro-2-propyl) phosphate [TCIPP], and tris(1,3-dichloro-2-propyl) phosphate [TDCIPP]). Exposure to most OPEs increased Mitotracker green intensity and reduced reactive oxygen species, total lipid droplet areas and lysosomal intensity. Potency ranking was done using the lowest benchmark concentration/administered equivalent dose method and toxicological prioritization index analyses to integrate all phenotypic endpoints. IPPP, TBOEP, and TPHP ranked as the most potent OPEs, whereas TMPP, TCIPP, and TDCIPP were relatively less bioactive. Confocal microscopic analysis demonstrated that IPPP reduced the co-localization of lipid droplets (PLIN2), lysosomes (LAMP1), and autophagosomes (p62), disrupting autophagy. In contrast, TBOEP rescued cells from bafilomycin A1-induced inhibition of autophagy and/or increased autophagic flux. Together, these data demonstrate that OPEs have adverse effects on HepG2 cells. Further, OPE-induced dysregulation of autophagy may contribute to the association between OPE exposure and adverse effects on liver lipid homeostasis.

Tracing Organophosphate Ester Pollutants in Hadal Trenches─Distribution, Possible Origins, and Transport Mechanisms.

Unraveling the mysterious pathways of pollutants to the deepest oceanic realms holds critical importance for assessing the integrity of remote marine ecosystems. This study tracks the transport of pollutants into the depths of the oceans, a key step in protecting the sanctity of these least explored ecosystems. By analyzing hadal trench samples from the Mariana, Mussau, and New Britain trenches, we found the widespread distribution of organophosphate ester (OPE) flame retardants but a complex transport pattern for the OPE in these regions. In the Mariana Trench seawater column, OPE concentrations range between 17.4 and 102 ng L-1, with peaks at depths of 500 and 4000 m, which may be linked to Equatorial Undercurrent and topographic Rossby waves, respectively. Sediments, particularly in Mariana (422 ng g-1 dw), showed high OPE affinity, likely due to organic matter serving as a transport medium, influenced by "solvent switching", "solvent depletion", and "filtering processes". Amphipods in the three trenches had consistent OPE levels (29.1-215 ng g-1 lipid weight), independent of the sediment pollution patterns. The OPEs in these amphipods appeared more linked to surface-dwelling organisms, suggesting the influence of "solvent depletion". This study highlights the need for an improved understanding of deep-sea pollutant sources and transport, urging the establishment of protective measures for these remote marine habitats.

Associations of Organophosphate Ester Flame Retardant Exposures during Pregnancy with Gestational Duration and Fetal Growth: The Environmental influences on Child Health Outcomes (ECHO) Program.

Widespread exposure to organophosphate ester (OPE) flame retardants with potential reproductive toxicity raises concern regarding the impacts of gestational exposure on birth outcomes. Previous studies of prenatal OPE exposure and birth outcomes had limited sample sizes, with inconclusive results. We conducted a collaborative analysis of associations between gestational OPE exposures and adverse birth outcomes and tested whether associations were modified by sex. We included 6,646 pregnant participants from 16 cohorts in the Environmental influences on Child Health Outcomes (ECHO) Program. Nine OPE biomarkers were quantified in maternal urine samples collected primarily during the second and third trimester and modeled as -transformed continuous, categorized (high/low/nondetect), or dichotomous (detect/nondetect) variables depending on detection frequency. We used covariate-adjusted linear, logistic, and multinomial regression with generalized estimating equations, accounting for cohort-level clustering, to estimate associations of OPE biomarkers with gestational length and birth weight outcomes. Secondarily, we assessed effect modification by sex. Three OPE biomarkers [diphenyl phosphate (DPHP), a composite of dibutyl phosphate and di-isobutyl phosphate (DBUP/DIBP), and bis(1,3-dichloro-2-propyl) phosphate] were detected in of participants. In adjusted models, DBUP/DIBP [odds ratio (OR) per ; 95% confidence interval (CI): 1.02, 1.12] and bis(butoxyethyl) phosphate (OR for high vs. ; 95% CI: 1.06, 1.46), but not other OPE biomarkers, were associated with higher odds of preterm birth. We observed effect modification by sex for associations of DPHP and high bis(2-chloroethyl) phosphate with completed gestational weeks and odds of preterm birth, with adverse associations among females. In addition, newborns of mothers with detectable bis(1-chloro-2-propyl) phosphate, bis(2-methylphenyl) phosphate, and dipropyl phosphate had higher birth weight-for-gestational-age -scores ( for detect vs. ); other chemicals showed null associations. In the largest study to date, we find gestational exposures to several OPEs are associated with earlier timing of birth, especially among female neonates, or with greater fetal growth. https://doi.org/10.1289/EHP13182.

An Initial Survey on Occurrence, Fate, and Environmental Risk Assessment of Organophosphate Flame Retardants in Romanian Waterways.

Organophosphate ester flame retardants (OPFRs) are ubiquitous organic pollutants in the environment and present an important preoccupation due to their potential toxicity to humans and biota. They can be found in various sources, including consumer products, building materials, transportation industry, electronic devices, textiles and clothing, and recycling and waste management. This paper presents the first survey of its kind in Romania, investigating the composition, distribution, possible sources, and environmental risks of OPFRs in five wastewater treatment plants (WWTPs) and the rivers receiving their effluents. Samples from WWTPs and surface waters were collected and subjected to extraction processes to determine the OPFRs using liquid chromatography with mass spectrometric detection. All the target OPFRs were found in all the matrices, with the average concentrations ranging from 0.6 to 1422 ng/L in wastewater, 0.88 to 1851 ng/g dry weight (d.w.) in sewage sludge, and 0.73 to 1036 ng/L in surface waters. The dominant compound in all the cases was tri(2-chloroisopropyl) phosphate (TCPP). This study observed that the wastewater treatment process was inefficient, with removal efficiencies below 50% for all five WWTPs. The environmental risk assessment indicated that almost all the targeted OPFRs pose a low risk, while TDCPP, TCPP, and TMPP could pose a moderate risk to certain aquatic species. These findings provide valuable information for international pollution research and enable the development of pollution control strategies.

Assessing emerging and priority micropollutants in sewage sludge: environmental insights and analytical approaches

The application of sewage sludge (SS) in agriculture, as an alternative to manufactured fertilizers, is current practice worldwide. However, as wastewater is collected from households, industries, and hospitals, the resulting sludge could contaminate land with creeping levels of pharmaceuticals, pesticides, heavy metals, polycyclic aromatic hydrocarbons, and microplastics, among others. Thus, the sustainable management of SS requires the development of selective methods for the identification and quantification of pollutants, preventing ecological and/or health risks. This study presents a thorough evaluation of emerging and priority micropollutants in SS, through the lens of environmental insights, by developing and implementing an integrated analytical approach. A quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction method, coupled with gas chromatography and liquid chromatography, was optimized for the determination of 42 organic compounds. These include organophosphorus pesticides, organochlorine pesticides, pyrethroid pesticides, organophosphate ester flame retardants, polybrominated diphenyl ethers, polychlorinated biphenyls, and polycyclic aromatic hydrocarbons. The optimization of the dispersive-solid phase for clean-up, combined with the optimization of chromatographic parameters, ensured improved sensitivity. Method validation included assessments for recovery, reproducibility, limit of detection (LOD), and limit of quantification (LOQ). Recoveries ranged from 59.5 to 117%, while LODs ranged from 0.00700 to 0.271 µg g-1. Application of the method to seven SS samples from Portuguese wastewater treatment plants revealed the presence of sixteen compounds, including persistent organic pollutants. The quantification of α-endosulfan, an organochlorine pesticide, was consistently observed in all samples, with concentrations ranging from 0.110 to 0.571 µg g-1. Furthermore, the study encompasses the analysis of agronomic parameters, as well as the mineral and metal content in SS samples. The study demonstrates that the levels of heavy metals comply with legal limits. By conducting a comprehensive investigation into the presence of micropollutants in SS, this study contributes to a deeper understanding of the environmental and sustainable implications associated with SS management.Graphical

Spatial and temporal patterns of organophosphate Esters flame retardants and plasticizers in airborne particles over the Mediterranean sea

We studied the co-occurrence of OPEs and other constituents in atmospheric particles at the two edges of the Mediterranean Sea, under the influence of the transport of polluted air from Europe and dust from the Sahara. The highest OPE concentrations were observed during the summer period in the East Mediterranean and in spring for the NW Mediterranean. The total average atmospheric concentration of Σ6OPEs in the NW Mediterranean was 2103 ± 2020 pg m−3 (n = 23) with EHDPP and TCPP to be the predominant OPEs, accounting on average for 46% and 37% of the total Ʃ6OPEs concentrations, respectively. The average concentration of Σ6OPEs in East Mediterranean was 156.4 ± 170.3 pg m−3 (n = 67) with TCPP showing the highest concentration (116.1 ± 92.8 pg m−3), followed by TCEP (67.5 ± 55.8 pg m−3). In both areas, OPEs were mostly associated with fossil fuel combustion and road traffic, while the air masses from Saharan desert influenced the concentration of EHDPP, TCEP in NW Mediterranean and the TCEP concentration levels in the East Mediterranean. The total annual deposition of reported OPEs to the Mediterranean basin was estimated to be 584 tonnes, accounting for about 8.5% of the total deposited anthropogenic phosphorus.

Organophosphate ester flame retardants and plasticizers in house dust and mental health outcomes among Canadian mothers: A nested prospective cohort study in CHILD

Organophosphate ester flame retardants and plasticizers (OPEs) are common exposures in modern built environments. Toxicological models report that some OPEs reduce dopamine and serotonin in the brain. Deficiencies in these neurotransmitters are associated with anxiety and depression. We hypothesized that exposure to higher concentrations of OPEs in house dust would be associated with a greater risk of depression and stress in mothers across the prenatal and postpartum periods.We conducted a nested prospective cohort study using data collected on mothers (n = 718) in the CHILD Cohort Study, a longitudinal multi-city Canadian birth cohort (2008–2012). OPEs were measured in house dust sampled at 3–4 months postpartum. Maternal depression and stress were measured at 18 and 36 weeks gestation and 6 months and 1 year postpartum using the Centre for Epidemiologic Studies for Depression Scale (CES-D) and Perceived Stress Scale (PSS). We used linear mixed models to examine the association between a summed Z-Score OPE index and continuous depression and stress scores. In adjusted models, one standard deviation increase in the OPE Z-score index was associated with a 0.07-point (95% CI: 0.01, 0.13) increase in PSS score. OPEs were not associated with log-transformed CES-D (β: 0.63%, 95% CI: −0.18%, 1.46%). The effect of OPEs on PSS score was strongest at 36 weeks gestation and weakest at 1 year postpartum.We observed small increases in maternal perceived stress levels, but not depression, with increasing OPEs measured in house dust during the prenatal and early postpartum period in this cohort of Canadian women. Given the prevalence of prenatal and postpartum anxiety and the ubiquity of OPE exposures, additional research is warranted to understand if these chemicals affect maternal mental health.

Integrative analysis of triphenyl phosphate: contextual interpretation of bladder cancer cohort.

In recent years, organophosphate ester flame retardants (OPFRs) have emerged as preferred alternatives to brominated flame retardants (BFRs) in materials such as building supplies, textiles, and furnishings. Simultaneously, a notable surge in bladder cancer incidences has been observed globally, particularly in developed nations, placing it as the 10th most prevalent cancer type. Among the extensive OPFRs, the linkage between triphenyl phosphate (TPP) and bladder cancer remains inadequately investigated. Hence, our study endeavors to elucidate this potential association. We sourced transcriptome profiles and TPP-related data from The Cancer Genome Atlas and Comparative Toxicogenomics databases. Using the ssGSEA algorithm, we established TPP-correlated scores within the bladder cancer cohort. Differentially expressed analysis enabled us to identify key genes in bladder cancer patients. We utilized the LASSO regression analysis, along with univariate and multivariate COX regression analyses to construct a prognostic prediction model. To uncover critical pathways involving key genes, we employed GSEA and GSVA enrichment analyses. Molecular docking analysis was performed to determine the binding capability between TPP and proteins. Our findings reveal that the TPP-centric risk model offers valuable prediction for bladder cancer cohorts. Furthermore, the reliability of this TPP-influenced risk model was verified through ROC curve analysis and survival studies. Intriguingly, TPP exposure appears to bolster the proliferation and invasiveness of bladder cancer cells. This study furnishes new insights into the possible benefits of minimizing TPP exposure for hindering bladder cancer progression.

Exposure to organophosphate ester flame retardants and plasticizers (OPEs) during pregnancy and autism-related outcomes

Exposure to organophosphate ester flame retardants and plasticizers (OPEs) during pregnancy and autism-related outcomes

Temporal trends and predictors of gestational exposure to organophosphate ester flame retardants and plasticizers

BackgroundOrganophosphate esters (OPEs), used as flame retardants and plasticizers, are chemicals of concern for maternal and infant health. Prior studies examining temporal trends and predictors of OPE exposure are primarily limited by small sample sizes. ObjectivesCharacterize temporal trends and predictors of OPE exposure biomarkers. MethodsWe determined urinary concentrations of eight biomarkers of OPE exposure at three timepoints during pregnancy for participants in the LIFECODES Fetal Growth Study (n = 900), a nested case-cohort recruited between 2007 and 2018. We examined biomarker concentrations, their variability during pregnancy, and temporal trends over the study period. In addition, we identified sociodemographic and pregnancy characteristics associated with biomarker concentrations. Analyses were conducted using both the within-subject pregnancy geometric means and biomarker concentrations measured at individual study visits. ResultsFive OPE biomarkers were detected in at least 60% of the study participants. Biomarkers were not strongly correlated with one another and intraclass correlation coefficients, measuring within-subject variability during pregnancy, ranged from 0.27 to 0.51. Biomarkers exhibited varying temporal trends across study years. For example, bis(1-chloro-2-propyl) phosphate (BCIPP) increased monotonically, whereas bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) and diphenyl phosphate (DPHP), displayed non-monotonic trends with concentrations that peaked between 2011 and 2014. We observed associations between sociodemographic characteristics and OPE biomarkers. In general, concentrations of most OPE biomarkers were higher among participants from racial and ethnic minority populations, participants who were younger, had higher pre-pregnancy body mass index (BMI), and less than a college degree. We observed consistent results using either averaged or visit-specific biomarker concentrations. SignificanceWe observed widespread exposure to several OPEs and OPE biomarkers displayed varying temporal trends in pregnant people from 2007 to 2018. Concentrations of most OPE biomarkers varied according to sociodemographic factors, suggesting higher burdens of exposure among participants with higher pre-pregnancy BMI, those belonging to racial and ethnic minority populations, and lower educational attainment.

Nontarget Identification of Novel Organophosphorus Flame Retardants and Plasticizers in Rainfall Runoffs and Agricultural Soils around a Plastic Recycling Industrial Park.

Plastic recycling and reprocessing activities may release organophosphate ester (OPE) flame retardants and plasticizers into the surrounding environment. However, the relevant contamination profiles and impacts remain not well studied. This study investigated the occurrence of 28 OPEs and their metabolites (mOPEs) in rainfall runoffs and agricultural soils around one of the largest plastic recycling industrial parks in North China and identified novel organophosphorus compounds (NOPs) using high-resolution mass spectrometry-based nontarget analysis. Twenty and twenty-seven OPEs were detected in runoff water and soil samples, with total concentrations of 86.0-2491 ng/L and 2.53-199 ng/g dw, respectively. Thirteen NOPs were identified, of which eight were reported in the environment for the first time, including a chlorine-containing OPE, an organophosphorus heterocycle, a phosphite, three novel OPE metabolites, and two oligomers. Triphenylphosphine oxide and diphenylphosphinic acid occurred ubiquitously in runoffs and soils, with concentrations up to 390 ng/L and 40.2 ng/g dw, respectively. The downwind areas of the industrial park showed elevated levels of OPEs and NOPs. The contribution of hydroxylated mOPEs was higher in soils than in runoffs. These findings suggest that plastic recycling and reprocessing activities are significant sources of OPEs and NOPs and that biotransformation may further increase the ecological and human exposure risk.

Organophosphate Esters (OPEs) Flame Retardants in Water: A Review of Photocatalysis, Adsorption, and Biological Degradation.

As a substitute for banned brominated flame retardants (BFRs), the use of organophosphate esters (OPEs) increased year by year with the increase in industrial production and living demand. It was inevitable that OPEs would be discharged into wastewater in excess, which posed a great threat to the health of human beings and aquatic organisms. In the past few decades, people used various methods to remove refractory OPEs. This paper reviewed the photocatalysis method, the adsorption method with wide applicability, and the biological method mainly relying on enzymolysis and hydrolysis to degrade OPEs in water. All three of these methods had the advantages of high removal efficiency and environmental protection for various organic pollutants. The degradation efficiency of OPEs, degradation mechanisms, and conversion products of OPEs by three methods were discussed and summarized. Finally, the development prospects and challenges of OPEs' degradation technology were discussed.

Exposure to Organophosphate Ester Flame Retardants in the Occupational Environment

Rationale: Flame retardants (FR) are commonly used in consumer products, electronics, and safety equipment. Organophosphate esters (OPEs) are a sub-class of FRs and are widely used in various industries. Occupational risk of exposure is expected for many workers in various industries. However, the evidence of occupational exposure to OPE FRs is limited.
 Objectives: This study aimed to summarize evidence of occupational exposure to OPE FRs.
 Methods: A scoping review was conducted using Scopus (April-2022) and Google Scholar (January-2022). Search terms included ""occupational"", ""exposure"", ""flame retardants"", ""organophosphate"" and similar. Studies with quantitative measures of OPE exposure in workplaces were retained. Information on sample types, exposure levels, routes of exposure, and contextual information was extracted and summarized.
 Results: To-date, 15 studies have met the inclusion criteria. Groups most frequently assessed for OPE exposure include workers in e-waste recycling facilities and constructions. Published studies have described inhalation exposure, incidental ingestion, and dermal absorption routes. Sampling methods included active air sampling, passive air sampling, biological sampling, and dermal sampling. Triphenyl phosphate (TPhP), Tris(2-chloroisopropyl) phosphate (TCIPP), and Tris(2-chloroethyl) phosphate (TCEP) were the three most common sampled OPEs.
 Conclusions: There is evidence of OPE exposure in a limited number of industries and occupations at levels higher than the general population. The adverse health effects associated with OPE exposure included reproductive complications, endocrine disruption, and potential carcinogenicity. More research is needed to understand the prevalence and level of occupational exposure to OPE FRs and the potential work-related health impacts.

Reproductive and developmental toxicity following exposure to organophosphate ester flame retardants and plasticizers, triphenyl phosphate and isopropylated phenyl phosphate, in Sprague Dawley rats.

Two organophosphate esters used as flame retardants and plasticizers, triphenyl phosphate (TPHP) and isopropylated phenyl phosphate (IPP), have been detected in environmental samples around the world. Human exposure primarily occurs via oral ingestion with reported higher concentrations in children. Currently, there are no data to evaluate potential risk from exposure to either TPHP or IPP during fetal development. These short-term perinatal studies in rats provide preliminary toxicity data for TPHP and IPP, including information on transfer to fetus/offspring and across the pup blood-brain barrier. In separate experiments, TPHP or IPP were administered via dosed feed at concentrations 0, 1000, 3000, 10 000, 15 000, or 30 000 ppm to time-mated Hsd:Sprague Dawley SD rats from gestation day (GD) 6 through postnatal day (PND) 28; offspring were provided dosed feed at the same concentration as their dam (PND 28-PND 56). TPHP- and IPP-related toxicity resulted in removal of both 30 000 ppm groups on GD 12 and 15 000 ppm IPP group after parturition. Body weight and organ weights were impacted with exposure in remaining dams. Reproductive performance was perturbed at ≥10 000 ppm TPHP and all IPP exposure groups. In offspring, both TPHP- and IPP-related toxicity was noted in pups at ≥10 000 ppm as well as reduction in bodyweights, delays in pubertal endpoints, and/or reduced cholinesterase enzyme activity starting at 1000 ppm TPHP or IPP. Preliminary internal dose assessment indicated gestational and lactational transfer following exposure to TPHP or IPP. These findings demonstrate that offspring development is sensitive to 1000 ppm TPHP or IPP exposure.

Effective degradation of organophosphate ester flame retardants and plasticizers in coastal sediments under high urban pressure

Empirical evidence of the effective degradation at environmentally relevant conditions of organophosphate esters (OPEs) flame retardants and plasticizers in coastal sediments from an impacted area in the NW Mediterranean Sea is provided. Half-lives varied from 23.3 to 77.0 (abiotic conditions) and from 16.8 to 46.8 days (biotic conditions), depending on the compound, highlighting the relevant role of microbial assemblages enhancing OPE degradation. After an immediate significant reduction of the bacterial abundance due to OPE addition to the sediment at the very beginning of the experiment, the observed biodegradation was associated to a general stimulation of the growth of the bacterial community during a first period, but without a marked change of the structure of the community. However, OPE contamination induced a decrease on the diversity of the bacterial community in the coastal sediment, noticeable after 14 days of incubation. It is likely that on one side the contamination had favoured the growth of some bacterial groups maybe involved in the biodegradation of these compounds but, on the other side, had also impacted some sensitive bacteria. The estimated half-lives fill a data gap concerning OPE degradation rates in marine sediments and will be valuable data for the refinement of OPE chemical risk assessment in marine environments, particularly on impacted sites.

West African e-waste-soil assessed with a battery of cell-based bioassays

Soil samples randomly taken from major e-waste sites in West Africa (Nigeria, Benin and Ghana) were examined for an extensive range of organic contaminants. Cytotoxicity measurements and assessment of activation of xeno-sensing receptors from fish (Atlantic cod) were employed as a battery of in vitro biological assays to explore the quality and toxicity profile of West African e-waste soil. The concentrations of the measured contaminants of emerging concerns (CECs) and persistent organic pollutants (POPs) in the e-waste soil differs significantly from the reference soil with chemical profiles typically dominated by legacy polybrominated diphenyl ethers (PBDEs) (405.8 μgkg−1) and emerging organophosphate ester flame retardant tris (1-chloro-2-propyl) phosphate (TCPP) (404 μgkg−1), in addition to the short chain perfluorobutane sulfonate (PFBS) (275.3 μgkg−1) and perfluorobutanoate (PFBA) (16 μgkg−1). The study revealed that perfluorooctanoic acid (PFOA) occurred only in e-waste soil from Ghana and ranged from 2.6 to 5.0 μgkg−1. Overall, non-polar e-waste soil-derived extracts had a stronger effect on COS-7 cell viability than the polar extracts and elutriates. The highest receptor activation was observed with single polar and non-polar extracts from the Nigeria and Benin sites, indicating hotspots with Er-, PPARa- and Ahr-agonist activities. Thus, the results obtained with our battery of in vitro biological assays underscored these e-waste sites as remarkably polluted spots with complex toxicity profiles of great concern for human and environmental health.

Prenatal exposure to mixtures of replacement flame retardant chemicals and children’s neuro-behavioral outcomes in a sample of children from socioeconomically disadvantaged communities

BACKGROUND. Organophosphate ester flame retardants (OPFRs) are persistent organic chemicals that are commercially applied to a wide variety of consumer products including electronics, building materials, foam-based furniture and children’s clothing that have individually been shown to adversely impact neurodevelopmental outcomes including hyperactivity symptoms, working memory, IQ and depressive symptoms. METHODS. We quantified nine prenatal OPFR urinary metabolites [DPHP, DNBP+DIBP, BDCIPP, BCEP, BBOEP, BCIPP, BMPP, BEHP and DPRP] by HPLC-MS/MS in samples from participants in the MADRES cohort--an ongoing pregnancy cohort in urban Los Angeles. Detection frequencies ranged from 99.8% for DPHP to 24.2% for DPRP. Specific-gravity adjusted OPFR metabolites detected in 60% or greater samples [DPHP, DNBP+DIBP, BDCIPP, BCEP, and BBOEP] were modeled continuously and log transformed, and values ≤ LOD were imputed as LOD/√2. The remaining four metabolites were modeled as detect/non-detect [BCIPP, BMPP, BEHP, and DPRP]. We assessed prenatal OPFR exposure associations with neurodevelopmental outcomes from the Child Behavior Checklist 1.5/5 in 151 predominantly Hispanic/Latino (~78%) children at age 3 years. RESULTS. We found significant associations between several OPFR metabolite concentrations and neurobehavioral outcomes in single metabolite adjusted models [e.g., a 10% increase in DNBP+DIBP concentration was associated with a 3.3% (95% CI 0.02%-6.49%) increase in internalizing symptoms score and a 4.8% (0.82%-8.95%) increase in DSM pervasive symptoms score]. However, exposure to a particular compound does not occur in isolation; thus it is critical that multiple exposures be considered jointly in human studies. We will discuss various analytical approaches to quantify the effects of environmental mixtures and apply them to understand multiple OPFR chemical exposure effects on early childhood neurobehavioral outcomes in a highly exposed, socioeconomically disadvantaged population. CONCLUSIONS. The application of mixtures methods will yield important insight into the conditional associations of co-exposures and enhance health risk assessment for child neurodevelopmental outcomes. KEYWORDS. Neurodevelopment, children, chemical mixtures

Organophosphate ester flame retardant exposure and perinatal outcomes

Background and Aims: Following a phase out of PBDE flame retardants in the mid-2000s due to concerns about toxicity, exposure to organophosphate ester (OPFRs) flame retardants increased, leading to increasing concerns regarding the toxicity of OPFRs. We hypothesize that prenatal exposure to OPFRs adversely affects outcomes at birth. Our overarching hypothesis is that prenatal exposure to OPFRs flame retardant chemicals adversely affects outcomes at birth. We propose to quantify prenatal exposure to a suite of flame retardants utilizing maternal urine collected during pregnancy to address our specific aims: 1) examine exposure trends over calendar time, and 2) investigate associations with perinatal outcomes, specifically low birth weight, preterm birth, and small for gestational age. Methods: We quantify prenatal exposure utilizing a single maternal urine collected during pregnancy, quantifying 9 OPFRs: Dipropyl phosphate (DPRP), Dibutyl phosphate + Di-isobutyl phosphate (DBUP_DIBP), bis(butoxyethyl) phosphate (BBOEP), bis(2-ethylhexyl) phosphate (BEHP), Bis(2-chlorethyl) phosphate (BCETP), Bis(1-chloro-2-propyl) phosphate (BCPP), Bis(1,3-dichloro-2-propyl) phosphate (BDCPP), Diphenyl phosphate (DPHP), and bis(2-methylphenyl) phosphate (BMPP). The study sample includes over 7000 pregnancies from 19 ECHO cohorts over 9 states. Outcomes include gestational age (continuous and categorized to consider preterm birth), birth weight (continuous and categorized to consider low birth weight), birthweight for gestational age (continuous and categorized to consider small for gestational age). Key confounders expected to be associated with both exposures and outcomes based on prior literature include cohort, maternal age, socioeconomic status (measured by education, marital status, income, or related variables), race/ethnicity, BMI, and year of birth. Results: The following compounds were detected in over 85% of the samples: BDCPP, DBUP_DIBP, and DPHP, while BBOEP, BCETP, and BCPP were detected in over 50% of samples. DPHP had the highest geometric mean concentration of 1.0 ng/mL, followed by BDCPP (0.86 ng/mL). Analysis of associations between exposures and outcomes is underway.