Toxicity assessment of organophosphate flame retardant triphenyl phosphate (TPHP) on intestines in mice.

Triphenyl phosphate (TPHP), one widely used organophosphate flame retardant, has attracted accumulating attention due to its high detection rate in human biological samples. Up to date, the effects of TPHP exposure on intestinal health remain unexplored. In this study, BALB/c mice were used as a model and exposed to TPHP at dose of 2, 10, or 50 mg/kg body weight for 28 days. We observed Crohn's disease-like features in ileum and ulcerative colitis disease-like features in colon, such as shorter colon length, ileum/colon structure impairment, intestinal epithelial cell apoptosis, enrichment of proinflammatory cytokines and immune cells, and disruption of tight junction. Furthermore, we found that TPHP induced production of reactive oxygen species and apoptosis in intestinal epithelial Caco-2 cells, accompanied by disruption of tight junction between cells. To understand the molecular mechanism underlying TPHP-induced changes in intestines, we build the adverse outcome pathway (AOP) framework based on Comparative Toxicogenomics and GeneCards database. The AOP framework revealed that PI3K/AKT and FoxO signaling pathway might be associated with cellular apoptosis, an increase in ROS production, and increased inflammation response in mouse ileum and colon tissues challenged with TPHP. These results identified that TPHP induced IBD-like features and provided new perspectives for toxicity evaluation of TPHP.

Environmentally relevant concentrations of tris (2-chloroethyl) phosphate (TCEP) induce hepatotoxicity in zebrafish (Danio rerio): a whole life-cycle assessment.

Tris (2-chloroethyl) phosphate (TCEP), a typical organophosphate flame retardant, is of increasingly great concern considering their ubiquitous presence in aquatic environments and potential ecotoxicity. The present work was aimed to investigate the potential growth inhibition and hepatic stress induced by whole life-cycle exposure to TCEP (0.8, 4, 20 and 100 µg/L) in zebrafish. The results revealed that the body length, body mass and hepatic-somatic index (HSI) of zebrafish were significantly declined after exposure to TCEP for 120 days. GPx activity and GSH content were increased in the liver of zebrafish treated with low concentrations (0.8 and 4 µg/L) of TCEP, while exposure to high concentrations (20 and 100 µg/L) of TCEP reduced antioxidative capacity and elevated lipid peroxidation (LPO) levels. Gene transcription analysis demonstrated that the mRNA levels of nrf2 were altered in a similar manner to the transcription of the downstream genes nqo1 and hmox1, suggesting that Nrf2-Keap1 pathway mediated TCEP-induced oxidative stress in zebrafish liver. In addition, TCEP exposure might alleviate inflammatory response through down-regulating transcription of inflammatory cytokines (il-1ß, il-6 and inos), and induce apoptosis via activating the p53-Bax pathway. Moreover, whole life-cycle exposure to TCEP caused a series of histopathological anomalies in zebrafish liver. Overall, our results revealed that lifetime exposure to environmentally relevant concentrations of TCEP could result in growth retardation and induce significant hepatotoxicity in zebrafish.

Childhood urinary organophosphate esters and cognitive abilities in a longitudinal cohort study.

The use of organophosphate esters (OPEs) as flame retardants, which has increased over the past two decades, raises concerns that OPEs may be harmful to humans, especially children. Animal studies and some human studies have reported that OPEs may adversely impact brain development, but few human studies evaluated OPE exposure during early childhood and neurodevelopmental outcomes. We aimed to fill this knowledge gap with the present study on urinary OPE metabolite concentrations at ages 1-5 years and cognitive abilities at 8 years. We used data of 223 children from the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort in Cincinnati, Ohio. The point estimates for bis-2-chloroethyl-phosphate (BCEP) and bis(1,3-dichloro-2-propyl)-phosphate (BDCIPP) in association with IQ tended to be small and positive, while the point estimates for diphenyl-phosphate (DPHP) were small and negative, with 95% CIs including the null. However, we did find that socioeconomic status (SES) variables modified associations between OPEs and child IQ, with adverse OPE-IQ associations being stronger in socioeconomically disadvantaged children than in others. We identified an additional 1- to 2-point decrease in Full Scale IQ for every log-unit increase in BDCIPP, BCEP, and DPHP among those with lower maternal education, non-white race, lower income, or living in more deprived neighborhoods. We observed similar results for the Perceptual Reasoning, Verbal Comprehension, and Working Memory Index Scores. We suspect that there is residual confounding related to socioeconomic disadvantage, which was not captured with the available SES variables typically used in epidemiologic studies.

Racial/ethnic and geographic differences in polybrominated diphenyl ether (PBDE) levels across maternal, placental, and fetal tissues during mid-gestation.

Prenatal polybrominated diphenyl ether (PBDE) exposures are a public health concern due to their persistence and potential for reproductive and developmental harm. However, we have little information about the extent of fetal exposures during critical developmental periods and the variation in exposures for groups that may be more highly exposed, such as communities of color and lower socioeconomic status (SES). To characterize maternal-fetal PBDE exposures among potentially vulnerable groups, PBDE levels were examined in the largest sample of matched maternal serum, placenta, and fetal liver tissues during mid-gestation among a geographically, racially/ethnically, and socially diverse population of pregnant women from Northern California and the Central Valley (n = 180; 2014-16). Maternal-fetal PBDE levels were compared to population characteristics using censored Kendall's tau correlation and linear regression. PBDEs were commonly detected in all biomatrices. Before lipid adjustment, wet-weight levels of all four PBDE congeners were highest in the fetal liver (p < 0.001), whereas median PBDE levels were significantly higher in maternal serum than in the fetal liver or placenta after lipid-adjustment (p < 0.001). We also found evidence of racial/ethnic disparities in PBDE exposures (Non-Hispanic Black > Latina/Hispanic > Non-Hispanic White > Asian/Pacific Islander/Other; p < 0.01), with higher levels of BDE-100 and BDE-153 among non-Hispanic Black women compared to the referent group (Latina/Hispanic women). In addition, participants living in Fresno/South Central Valley had 34% (95% CI: - 2.4 to 84%, p = 0.07) higher wet-weight levels of BDE-47 than residents living in the San Francisco Bay Area. PBDEs are widely detected and differentially distributed in maternal-fetal compartments. Non-Hispanic Black pregnant women and women from Southern Central Valley geographical populations may be more highly exposed to PBDEs. Further research is needed to identify sources that may be contributing to differential exposures and associated health risks among these vulnerable populations.

Dietary exposure assessment of a nursing mother-infant cohort to legacy and novel brominated flame retardants: Results of a 3-day duplicate diet study in Beijing, China.

In a 3-day duplicate diet study of a nursing mother-infant cohort (n = 20), the levels of polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCDD), and 5 novel brominated flame retardants (BFRs) were measured in 60 24-h duplicate diet samples and 20 breast milk samples provided by the mothers. The dietary BFR intake and related health risks of the mothers and their babies due to food consumption or human milk ingestion were subsequently assessed. At median concentrations of 284, 264 and 177 pg/g wet weight (ww) in the diet, decabrominated diphenyl ethers (BDE-209), decabromodiphenyl ethane (DBDPE) and HBCDD were predominant among the total BFRs. In human milk, HBCDD was the most abundant BFR, followed by BDE-209 and DBDPE, which indicates that BDE-209 and HBCDD have remained ubiquitous in the environment because of their continuous production and use in China. Meanwhile, concentrations of DBDPE were comparative to those of PBDEs and HBCDD in both diet and human milk, and DBDPE also had much higher concentrations than any other NBFRs, which indicates that the BFR consumption pattern in China is shifting from legacy BFRs to NBFRs. The median estimated dietary intakes (EDIs) of BDE-209, HBCDD and DBDPE for the mothers were 6.83, 3.73 and 5.44 ng/kg bw/day, respectively, and EDIs for their nursing babies were 24.7, 41.9 and 7.83 ng/kg bw/day, respectively. The nursing infants showed higher BFR body burden than the mothers. However, the EDIs obtained for both mothers and their babies discloses a low health risk to this mother-infant cohort.

Assessment of organophosphate flame retardants in Mediterranean Boops boops and their relationship to anthropization levels and microplastic ingestion.

Plastic litter pollution is increasing in the seas and oceans worldwide, raising concern on the potential effects of plasticizer additives on marine fauna. In this study, muscle samples of 30 bogues (Boops boops; Linneaus, 1758) from the North Western Mediterranean Sea were analysed to assess the concentrations of 19 organophosphate flame retardant (OPFR) compounds and to inspect any relationship with microplastic ingestion and relative levels of anthropization. Out of the 19 OPFRs analysed, 6 compounds were detected, being tri-n-butyl phosphate (TNBP), 2-ethylhexyldiphenyl phosphate (EHDPP) and triphenylphosphine oxide (TPPO) the most abundant. As expected, OPFR concentrations were higher in samples collected off the most anthropized area of the city of Barcelona than in those from the Cap de Creus Marine Protected Area, while no significant correlation was detected between OPFR concentrations and microplastic ingestion. The results of this manuscript provide a first evidence of OPFR presence in the muscle of the bogue and identify the coastal area off Barcelona as a possible concentration area for contaminants, further supporting the use of the bogue as an indicator species of plastic pollution in the Mediterranean Sea.

Tetrabromobisphenol A and hexabromocyclododecane isomers in breast milk from the general population in Beijing, China: Contamination levels, temporal trends, nursing infant's daily intake, and risk assessment.

Two currently used brominated flame retardants (BFRs), α, ß, γ-hexabromocyclododecane (HBCDD) and tetrabromobisphenol A (TBBPA), were measured in 111 breast milk samples from 37 Beijing mothers. Each mother provided one milk sample per month for 3 months. HBCDD was detected in almost all samples, and the median level reached 5.67 ng g-1 lipid weight (lw). α- HBCDD was the most abundant isomer (median: 4.23 ng g-1 lw), followed by γ- and ß-HBCDD. For TBBPA, a relatively lower detecting frequency (64%) and contamination level (median: 1.57 ng g-1 lw) were obtained. A comparison to our previous study revealed that the occurrence of TBBPA and HBCDD in Beijing human milk significantly rose from 2011 to 2014, whereas another commonly used class of BFRs, polybrominated diphenyl ethers (PBDEs), showed significantly decreased during this period. However, a comparison among currently used BFRs showed that levels of some BFRs, such as HBCDD, surpassed those of PBDEs, which indicated that PBDEs were no longer the primarily used BFR in China. However, no significant temporal trends for BFR levels were observed over the 3 months of lactation. Daily intakes of TBBPA and HBCDD were calculated for nursing infants and the median TBBPA and HBCDD intakes via breastfeeding were 6.62 and 26.4 ng kg-1 bw day-1, respectively. These values were several times higher than those for adults via food consumption. However, risk assessment using the margin of exposure approach indicated that intakes of TBBPA and HBCDD via breastfeeding can scarcely cause significant health risks to infants.

Polybrominated diphenyl ethers and novel brominated flame retardants in human milk from the general population in Beijing, China: Occurrence, temporal trends, nursing infants' exposure and risk assessment.

The levels of eight polybrominated diphenyl ether (PBDE) congeners, and six novel brominated flame retardants (NBFRs) were determined in human milk collected from Beijing, China in 2014. The tested 111 samples were collected from 37 mothers, and each donor provided one milk sample per month for 3 months after childbirth. Levels of ∑PBDEs (total tri- to deca-BDEs) were in the range of 0.288 to 22.2 ng g-1 lw (lipid weight). BDE-209, with a median level of 2.2 ng g-1 lw, was the predominant congener. Decabromodiphenyl ethane (DBDPE), as an NBFR and a substitute for deca-BDE, was found to be the most abundant BFR in all tested human milk (median:5.96 ng g-1 lw). This result might suggest that the predominantly consumed BFRs in China have changed from PBDEs to PBDE substitutes. Additionally, a comparison to our previous studies conducted in 2005 and 2011 revealed that levels of tri- to hepta-BDEs showed significant reduction from 2005 to 2014, whereas levels of BDE-209 showed no significant variation from 2011 to 2014. Temporal trends of BFR levels over the three months of lactation were also investigated, and no significant changes were found in concentration with time over the three months lactation. For nursing infants up to 6 months old, the median lower bound of daily BFR intakes via human milk ingestion ranged from zero for 2,3-dibromopropyl-2,4,6-tribromophenyl ether (DPTE) and 1,2-bis(2,4,6-tribromophenoxy)-ethane (BTBPE) to 18.7 ng kg-1 bodyweight day-1 for DBDPE. Although the daily dietary BFR intake for nursing infants was found to be much higher than that for adults, the risk assessment evaluated by the margin of exposure (MOE) approach revealed that dietary BFR intake for nursing infants was unlikely to pose significant health risks.

Urinary biomarkers for assessment of human exposure to monomeric aryl phosphate flame retardants.

While monomeric aryl organophosphate flame retardants (m-aryl-OPFRs) are used worldwide in a variety of consumer products, specific biomarkers for epidemiologic studies are lacking. To explore the potential of urinary hydroxylated metabolites of m-aryl-OPFRs as the biomarkers, we detected triphenyl phosphate (TPHP), 2-ethylhexyl diphenyl phosphate (EHDPP), and tricresyl phosphate (TCrP) in 259 whole blood samples and their 5 hydroxylated and 2 diester metabolites in the paired urine samples from the general population. 2-Ethyl-5-hydroxyhexyl diphenyl phosphate (5-OH-EHDPP), 4-hydroxyphenyl diphenyl phosphate (4-OH-TPHP), and 3-hydroxy-4-methylphenyl di-p-tolyl phosphate (3-OH-MDTP) were detected in >80% of urine samples after enzymatic hydrolysis of conjugates, and their concentrations showed significant positive correlations with the blood concentrations of their corresponding parent compounds, respectively. To characterize the temporal reliability, the m-aryl-OPFRs metabolites were also determined in urine samples repeated nine times from six volunteers over 3 months. Urinary 5-OH-EHDPP showed strong temporal reliability (creatinine-corrected intraclass correlation coefficients (ICCs), 0.77; 95% confidence interval [CI], 0.58 to 0.90), and urinary 3-OH-MDTP (creatinine-corrected ICC, 0.52; 95% CI, 0.37 to 0.87) and 4-OH-TPHP (0.56; 95% CI, 0.32 to 0.80) showed moderate-to-strong temporal reliability, while relatively weak temporal reliability was found for urinary DPHP (creatinine-corrected ICC, 0.37; 95% CI, 0.12 to 0.62). This study confirmed specific, reliable, and frequently detected biomarkers for TPHP and EHDPP and developed new biomarker of TCrP for future epidemiological research on health effects of m-aryl-OPFRs.

Melamine and its derivatives in dog and cat urine: An exposure assessment study.

Melamine is a nitrogen-containing organic compound that is used in a wide range of products, including paints, plastics, and paper, as a flame retardant. A few studies have reported the occurrence of melamine and its derivatives in pet food, following a number of deaths of cats and dogs from kidney failure in 2007, which was attributed to melamine contamination in ingredients used in pet food. Nevertheless, studies that report the occurrence of melamine and its derivatives in pet urine are scarce. In this study, we measured melamine and its derivatives (i.e., ammeline, ammelide, and cyanuric acid) in dog (n = 30) and cat (n = 30) urine collected from Albany, New York, USA, during March through July 2017. The mean (±SD) concentrations of melamine, ammeline, ammelide, and cyanuric acid in dog urine were 21.1 ±â€¯51.2, 2.3 ±â€¯3.8, 9.9 ±â€¯1 0.4, and 79.0 ±â€¯105 ng/mL, respectively; the corresponding concentrations in cats were 21.4 ±â€¯26.1, 1.2 ±â€¯2.5, 6.1 ±â€¯3.9, and 105 ±â€¯94.6 ng/mL, respectively. No significant difference was observed in urinary concentrations of melamine derivatives between cats and dogs. Age and gender were important determinants of the concentrations of the target chemicals in cats and dogs. Cumulative daily intake of melamine and its derivatives was calculated on the basis of urinary concentrations and was found to be 10-500-fold below the tolerable daily intake.

A Human Mixture Risk Assessment for Neurodevelopmental Toxicity Associated with Polybrominated Diphenyl Ethers Used as Flame Retardants.

BACKGROUND: The European Food Safety Authority recently concluded that the exposure of small children (1-3 y old) to brominated diphenyl ether (BDE)-99 may exceed acceptable levels defined in relation to neurodevelopmental toxicity in rodents. The flame retardant BDE-209 may release BDE-99 and other lower brominated BDEs through biotic and abiotic degradation, and all age groups are exposed not only to BDE-209 and -99 but also to a cocktail of BDE congeners with evidence of neurodevelopmental toxicity. The possible risks from combined exposures to these substances have not been evaluated. OBJECTIVES: We performed a congener-specific mixture risk assessment (MRA) of human exposure to combinations of BDE-209 and other BDEs based on estimated exposures via diet and dust intake and on measured levels in biologic samples. METHODS: We employed the Hazard Index (HI) method by using BDE congener-specific reference doses for neurodevelopmental toxicity. RESULTS: Our HI analysis suggests that combined exposures to polybrominated diphenyl ethers (PBDEs) may exceed acceptable levels in breastfeeding infants (0-3 mo old) and in small children (1-3 y old), even for moderate (vs. high) exposure scenarios. Our estimates also suggest that acceptable levels of combined PBDEs may be exceeded in adults whose diets are high in fish. Small children had the highest combined exposures, with some estimated body burdens that were similar to body burdens associated with developmental neurotoxicity in rodents. CONCLUSIONS: Our estimates corroborate reports from several recent epidemiological studies of associations between PBDE exposures and neurobehavioral outcomes, and they support the inclusion of BDE-209 in the persistent organic pollutant (POP) convention as well as the need for strategies to reduce exposures to PBDE mixtures, including maximum residue limits for PBDEs in food and measures for limiting the release of PBDEs from consumer waste. https://doi.org/10.1289/EHP826.

Risk assessment and Biomonitoring Equivalent for 2-ethylhexyl-2,3,4,5 tetrabromobenzoate (TBB) and tetrabromobenzoic acid (TBBA).

2-ethylhexyl-2,3,4,5 tetrabromobenzoate (TBB) is used as a flame retardant. Biomonitoring for TBB exposures include the metabolite, tetrabromobenzoic acid (TBBA), in urine. We derived a Reference Dose (RfD) for TBB and a Biomonitoring Equivalent (BE) for TBBA in urine. Three longer-term studies of oral gavage dosing of a commercial mixture BZ-54 (which includes 70% TBB) in rats were evaluated for deriving the RfD. The 95% lower confidence limits on the BMD associated with a 1 SD change from the mean (BDMLSD) values ranged from 77 to 134 mg/kg-day. The mean BMDLSD value of 91 mg/kg-day for maternal body weight changes was selected as the appropriate point of departure (POD), corresponding to a human equivalent dose (PODHEC) of 25 mg/kg-day. A total composite uncertainty factor (UF) of 300 yields an RfD of 0.08 mg/kg-day. A urinary mass excretion fraction (Fue) of 0.6 for TBBA following oral doses of TBB in rats was used to calculate BEs for TBBA in urine of 2.5 mg/L and 2.5 mg/g cr. Mean (5.3 × 10-6 mg/L) and maximum (340 × 10-6 mg/L) levels of TBBA measured in urine from human volunteers reported in the literature indicates margins of safety (MOS) are approximately 450,000 and 7,000, respectively.

In vivo assessment of dermal adhesion, penetration, and bioavailability of tetrabromobisphenol A.

Individuals are exposed to brominated flame retardants (BFRs), including tetrabromobisphenol A (TBBPA), on a daily basis because of their widespread usage. These compounds may have adverse effects on human health. In the present study, dermal absorption experiments were conducted in vivo to predict the adhesion, penetration, and bioavailability of TBBPA. TBBPA was administered to Wistar rats for 6 h by repeated dermal exposure at doses of 20, 60, 200, and 600 mg of TBBPA per kg of body weight (bw). The skin adhesion coefficient (AC) was calculated using a difference-value method and ranged from 0.12 to 3.25 mg/cm2 and 0.1 to 2.56 mg/cm2 for the male and female rats, respectively. The adhesion rate was 70.92%. According to Fick's first law of diffusion, the diffusion constant (D) was 1.4 × 10-4 cm2/h and the permeation coefficient (Kp) was 1.26 × 10-5 cm/h for TBBPA. TBBPA levels in the blood, urine, and feces of the male rats were significantly higher than those in the female rats. The dermal bioavailability of TBBPA was 24.71% for male rats and 20.05% for female rats 24 h after exposure.

Preliminary assessment on the bioaccessibility of contaminants of emerging concern in raw and cooked seafood.

A preliminary assessment of the bioaccessibility of contaminants of emerging concern (CeCs), including perfluorinated compounds (PFCs; i.e. PFOS and PFUnA), brominated flame retardants (BFRs; i.e. BDE47, BDE100, α-HBCD) and pharmaceuticals and personal care products (PPCPs; i.e. venlafaxine, methylparaben and UV-filter OC) was performed in seafood species available in the European markets. Additionally, the effect of steaming on CeCs bioaccessibility was also investigated for the first time. Overall, steaming affected differentially contaminants' concentrations, for instance, decreasing PFOS levels in flounder, but increasing both BDE47 and BDE100. CeCs bioaccessibility varied according to seafood species and contaminant group, i.e. in general, lower bioaccessibility values were obtained for PBDEs (<70%, except for mackerel), while PFCs and PPCPs revealed higher bioaccessibility percentages (between 71 and 95%). The lowest bioaccessibility value was obtained for α-HBCD (mussel; 14%), whereas the highest percentage was observed in venlafaxine (mullet; 95%). Our preliminary study reports also, for the first time, the effects of steaming on CeCs bioaccessibility. In most cases, bioaccessibility was not affected by cooking, however, a decrease was observed in PBDEs and venlafaxine bioaccessibility in steamed mussels and mullet, respectively, thus lowering the potential health risks associated with seafood consumption.

The first exposure assessment of legacy and unrestricted brominated flame retardants in predatory birds of Pakistan.

The exposure to legacy polybrominated diphenyl ethers (PBDEs), hexabromocyclododecanes (HBCDDs) and unrestricted 1,2-bis (2,4,6-tribromophenoxy) ethane (BTBPE), bis (2-ethylhexyl)-2,3,4,5-tetrabromophthalate (BEH-TEBP) and 2-ethylhexyl-2,3,4,5-tetrabromo-benzoate (EH-TBB) was examined in tail feathers of 76 birds belonging to ten predatory species inhabiting Pakistan. In addition, different feather types of six individuals of Black kite (Milvus migrans) were compared for their brominated flame retardant (BFR) levels. Black kite was found to be the most contaminated species with a median (minimum-maximum) tail feather concentration of 2.4 (0.70-7.5) ng g-1 dw for ∑PBDEs, 1.5 (0.5-8.1) ng g-1 dw for ∑HBCDDs and 0.10 ( 0.05 for both). Similarly, no significant concentration differences were observed among different feather types (all P > 0.05) suggesting their similar exposure. While variables such as species, trophic guild and δ15N values were evaluated as major predictors for BFR accumulation in the studied species, we predict that combined effects of just mentioned factors may govern the intra- and interspecific differences in BFR contamination profiles. We urge for further investigation of BFR exposure and potential toxicological effects in predatory birds from Asia with a more extensive sample size per species and location.

Biotransformation of three phosphate flame retardants and plasticizers in primary human hepatocytes: untargeted metabolite screening and quantitative assessment.

Tris(2-butoxyethyl) phosphate (TBOEP), triphenyl phosphate (TPHP) and tris(1-chloro-2-propyl) phosphate (TCIPP) are current high-volume organophosphate flame retardants/plasticizers (PFRs) and are abundant in the indoor environment. While recent in vitro research has indicated potential toxic effects in the endocrine system, biotransformation of these compounds is still underexplored. In this study, we aimed to characterize the metabolite formation for three PFRs in primary human hepatocytes, an in vitro system that mimics in vivo liver metabolism more closely than hepatic subcellular fractions or cell lines. Cryopreserved human hepatocytes were thawed and suspended in media with 50 µm TBOEP or TCIPP, or 20 µm TPHP up to 2 h. Extracts were analyzed by liquid chromatography-quadrupole-time-of-flight-mass spectrometry. Quantification of biotransformation products in hepatocytes exposed for 2 h revealed that bis(1-chloro-2-propyl) phosphate and diphenyl phosphate corresponded to less than half of the depletion of TCIPP and TPHP, respectively, while bis(2-butoxyethyl) 2-hydroxyethyl phosphate compared to 40-66% of the depletion of TBOEP. Other metabolite structures of these PFRs were produced at 4- to 10-fold lower rates. These findings help interpret biological levels of the major metabolites and relate it to levels of their parent PFR. Percentage of substrate depletion was largest for TBOEP followed by comparable values for TPHP and TCIPP, indicating that hepatic clearance of TPHP and TCIPP would be slower than that of TBOEP. The resulting higher levels and longer presence of TPHP in the circulation after exposure, would allow TPHP a larger time window to exert its suspected adverse effects compared to TBOEP. Copyright © 2016 John Wiley & Sons, Ltd.

Assessment of human hair as an indicator of exposure to organophosphate flame retardants. Case study on a Norwegian mother-child cohort.

A major challenge of non-invasive human biomonitoring using hair is to assess whether it can be used as an indicator of exposure to Flame Retardants, such as Organophosphate Flame Retardants (PFRs), since the contribution of atmospheric deposition (air and/or dust) cannot be neglected. Therefore, the aim of this study was to evaluate the suitability of using human hair more thoroughly by comparison of (i) levels of PFRs in human hair (from 48 mothers and 54 children), with levels measured in dust and air in their respective households; and (ii) levels of selected PFRs in hair with the levels of corresponding PFR metabolites in matching urine samples collected simultaneously. Most PFRs (tri-n-butyl phosphate (TNBP), 2-ethyl-hexyldiphenyl phosphate (EHDPHP), tri-phenyl phosphate (TPHP), tri-iso-butyl phosphate (TIBP), and tris(2-butoxyethyl) phosphate (TBOEP)) were detected in all human hair samples, tris(2-ethylhexyl) phosphate (TEHP) and tris(1,3-dichloro-iso-propyl) phosphate (TDCIPP) in 93%, tri-cresyl-phosphate (TCP) in 69% and tris(2-chloroethyl) phosphate (TCEP) in 21% of the samples. Levels of individual PFRs ranged between <1 and 3744 ng/g hair and were lower than in indoor dust from the participants' homes. Several statistically significant associations between PFR levels in human hair and PFR levels in house dust and/or air were found, e.g. Spearman correlation (rS = 0.561, p < 0.05) between TBOEP in children's hair and in indoor air. Also, associations were found between TDCIPP in hair and its metabolite bis(1,3-dichloro-iso-propyl) phosphate (BDCIPP) in urine; they were stronger for children (e.g. Pearson correlation rP = 0.475; p = 0.001) than for mothers (rP = 0.395, p = 0.01). Levels of diphenyl phosphate (DPHP) in mothers' and children's urine were slightly correlated (rS = 0.409, p = 0.008), suggesting similar sources of exposure. To the best of our knowledge, this is the first study with such design and our findings might help to understand human exposure to and body burdens of PFRs.

Evaluation of in vitro vs. in vivo methods for assessment of dermal absorption of organic flame retardants: a review.

There is a growing interest to study human dermal exposure to a large number of chemicals, whether in the indoor or outdoor environment. Such studies are essential to predict the systemic exposure to xenobiotic chemicals for risk assessment purposes and to comply with various regulatory guidelines. However, very little is currently known about human dermal exposure to persistent organic pollutants. While recent pharmacokinetic studies have highlighted the importance of dermal contact as a pathway of human exposure to brominated flame retardants, risk assessment studies had to apply assumed values for percutaneous penetration of various flame retardants (FRs) due to complete absence of specific experimental data on their human dermal bioavailability. Therefore, this article discusses the current state-of-knowledge on the significance of dermal contact as a pathway of human exposure to FRs. The available literature on in vivo and in vitro methods for assessment of dermal absorption of FRs in human and laboratory animals is critically reviewed. Finally, a novel approach for studying human dermal absorption of FRs using in vitro three-dimensional (3D) human skin equivalent models is presented and the challenges facing future dermal absorption studies on FRs are highlighted.

Dietary exposure and screening-level risk assessment of polybrominated diphenyl ethers (PBDEs) and dechloran plus (DP) in wheat, rice, soil and air along two tributaries of the River Chenab, Pakistan.

No scientific report is available for screening level-risk assessment of newly emerging contaminants, including polybrominated diphenyl ethers (PBDEs) and dechloran plus (DP) in food crops and environmental compartments of Pakistan. Dietary exposure of PBDEs and DP via food crops; screening levels, spatial distribution pattern of PBDEs and DP in air, soil, wheat and rice were assessed along the stretch of upstream feeding tributaries (Nullah Aik and Nullah Palkhu), River Chenab, Pakistan. ∑PBDE levels in air, soil, wheat and rice ranged between 0.59 and 7.80pgm(-3), 6.88 and 37.7ngg(-1), 0.30ngg(-1) and 1.43ngg(-1) and 0.07 and 46.0ngg(-1), respectively. ∑DP concentrations calculated in air, soil, wheat and rice ranged between 0.80 and 0.10pgm(-3), 0.17 and 2.61ngg(-1), 0.90 and 0.49ngg(-1) and 0.00 and 12.5ngg(-1), respectively. The trend of PBDEs and DP distribution pattern was found as follows; industrial/urban areas>industrial/peri-urban areas>agricultural/rural areas. Estimated daily intake (EDI) for wheat and rice was ranged between 0.002 and 0.035pgkg(-1)d(-1) and 0.033 and 0.680pgkg(-1)d(-1). Human health risks for adults on the basis of EDI were lower than the recommended MRL (minimal risk level) and lowest observed adverse effect of level (LOAEL).

The occurrence of organic contaminants in European eel (Anguilla anguilla) in Poland: an environmental quality assessment.

The objective of the present study was to provide information on the levels of pollutants in the tissues of eels caught in Polish waters. The contaminants included in the study are those which have not yet been widely studied in eel stocks, but which arouse concern in relation to the environment. An overview of the pollutant levels in eels caught in other European waters was also conducted. The results are evaluated in terms of environmental quality and consumer health. The mean concentrations of ΣPBDEs and ΣHBCDs in muscles of eels sampled in Polish waters were between 1 and 2 ng g(-1) ww. The mean TBT concentrations were between 2 and 4 ng g(-1)ww with the exception of samples from the Szczecin Lagoon, in which the mean TBT concentration was about tenfold higher.