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Keywords: visible light; 3-methylindole; tryptamine; diphenyl diselenide; diphenyl phosphate EN visible light 3-methylindole tryptamine diphenyl diselenide diphenyl phosphate 3685 3692 8 10/19/23 20231102 NES 231102 Graph The incorporation of selenium into organic scaffolds is not only pivotal for understanding redox processes of biological system, [1] but also plays an important role in pharmaceuticals [5] wherein selenium-containing molecules serve as synthetic intermediates [6] and catalysts for the preparation of various bioactive compounds. When an additive diphenyl phosphate (DPP) was added, formation of desired C-2 Cbz-tryptamine selenide adduct was observed in good yield (entry 2). Transition-metal-catalyzed C2/C3-H activation of indole core (tryptamines) offers robust synthetic strategies to deliver functionalized cores. SP 1 sp H NMR (500 MHz, CDCl SB 3 sb ): = 8.56-8.46 (m, 1 H), 7.69 (d, I J i = 7.9 Hz, 1 H), 7.62 (d, I J i = 7.0 Hz, 1 H), 7.34 (d, I J i = 8.3 Hz, 1 H), 7.27 (s, 1 H), 7.23-7.18 (m, 5 H), 7.16 (s, 1 H), 4.76 (s, 1 H), 4.59 (dt, I J i = 11.6, 6.4 Hz, 2 H), 3.99 (q, I J i = 5.1, 3.1 Hz, 2 H), 3.86 (d, I J i = 4.0 Hz, 2 H), 3.24 (t, I J i = 7.1 Hz, 2 H), 2.32 (d, I J i = 3.6 Hz, 2 H), 2.22 (d, I J i = 4.7 Hz, 2 H), 1.96-1.91 (m, 3 H), 1.82-1.74 (m, 6 H), 1.68-1.66 (m, 2 H), 1.55-1.51 (m, 5 H), 1.30-1.24 (m, 4 H), 1.07 (dd, I J i = 14.4, 3.2 Hz, 2 H), 0.92 (s, 3 H), 0.67 (s, 3 H). [Extracted from the article]

Triphenyl phosphate (TPHP) is a widely used flame retardant and plasticizer and has been detected extensively in environmental media, wildlife and human bodies. Several epidemiological and animal studies have revealed that TPHP exposure is positively associated with glucose homeostasis disruption and diabetes. However, the effects of TPHP on hepatic glucose homeostasis and the underlying mechanisms remain unclear. The present work aimed to investigate the cytotoxicity and glucose metabolism disruption of TPHP and its metabolite diphenyl phosphate (DPHP) within hepatocytes. The cell viability assay undertaken on human normal liver (L02) cells showed that TPHP exhibited more potent hepatotoxicity than DPHP. RNA sequencing (RNA-seq) data showed that TPHP and DPHP presented different modes of toxic action. Insulin resistance is one of the predominant toxicities for TPHP, but not for DPHP. The insulin-stimulated glucose uptake and glycogen synthesis were impaired by TPHP, while DPHP exhibited no significant impairment on these factors. TPHP exposure induced endoplasmic reticulum (ER) stress, and the ER stress antagonist 4-PBA restored the impairment of insulin-stimulated glucose uptake and glycogen synthesis induced by TPHP. TPHP could also induce liver ER stress and insulin resistance in mice. Taken together, the results suggested that TPHP induces more potent insulin resistance through ER stress than its metabolite DPHP.

Background: Organophosphate esters (OPEs) are a class of flame retardants in common use. OPEs can easily leach from materials, resulting in human exposure. Increasing concentrations have been reported in human populations over the past decade. Recent studies have linked prenatal OPE exposure to hyperactivity and attention problems in children. Such behaviors are often found among children with attention-deficit hyperactivity disorder (ADHD), however, no study has investigated OPEs in relation to clinically assessed ADHD. Objective: To evaluate prenatal exposure to OPEs as risk factors for clinically assessed ADHD using a case-cohort study nested within the Norwegian Mother, Father, and Child Cohort Study (MoBa). Methods: We included in the case group 295 ADHD cases obtained via linkage with the Norwegian Patient Registry, and the sub-cohort group 555 children sampled at baseline, irrespective of their ADHD case status. Prenatal concentrations of OPE metabolites were measured in maternal urine collected at 17 weeks of gestation, and included diphenyl phosphate (DPHP), di-n-butyl phosphate (DNBP), bis(2-butoxyethyl) hydrogen phosphate (BBOEP), and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP). We estimated risk ratios and the corresponding 95% confidence intervals [95% CI] using logistic regression, adjusting for season of urine collection, child sex, birth year, and maternal depression, education, and sum of urinary di(2-ethylhexyl) phthalate metabolites (∑DEHP) concentration during pregnancy. To assess the overall impact of simultaneously decreasing exposure to all chemical constituents of an OPE-phthalate mixture, quantile based g-computation was implemented. The mixture constituents included OPE and phthalate metabolites commonly detected in our study. In all models, we considered effect measure modification by child sex and polymorphisms in genes encoding paraoxonase 1 (PON1) and cytochrome P450 (P450) enzymes. Mediation analysis was conducted using thyroid function biomarkers estimated from maternal blood collected at 17 weeks of gestation. Results: DPHP was detected in nearly all samples (97.2%), with a higher geometric mean among the case group (0.70 µg/L) as compared to the sub-cohort (0.52 µg/L). DNBP was commonly detected as well (93.8%), while BBOEP (52.9%) and BDCIPP (22.9%) were detected less frequently. A higher risk of ADHD was observed in children with greater than median exposure to DPHP during pregnancy (risk ratio: 1.38 [95% CI: 0.96, 1.99]), which was slightly higher among girls (2.04 [1.03, 4.02]) and children of mothers with PON1 Q192R genotype QR (1.69 [0.89, 3.19]) or PON1 Q192R genotype RR (4.59 [1.38, 15.29]). The relationship between DPHP and ADHD (total risk ratio: 1.34 [0.90, 2.02]) was partially mediated through total triiodothyronine to total thyroxine ratio (natural direct effect: 1.29 [0.87, 1.94]; natural indirect effect: 1.04 [1.00, 1.10]; 12.48% mediated). We also observed an elevated risk of ADHD in relation to BDCIPP detection during pregnancy (1.50 [0.98, 2.28]). We did not observe notable differences in ADHD by DNBP (0.88 [0.62, 1.26]) or BBOEP (1.03 [0.73, 1.46]) during pregnancy. Simultaneously decreasing all constituents of common-detect OPE-phthalate mixture, specifically DPHP, DNBP, and 6 phthalate metabolites, by a quartile resulted in an ADHD risk ratio of 0.68 [0.64, 0.72]. Conclusion: Prenatal exposure to DPHP and BDCIPP may increase the risk of ADHD. For DPHP, we observed potential modification by child sex and maternal PON1 Q192R genotype and partial mediation through maternal thyroid hormone imbalance at 17 weeks gestation.

This paper presents the findings of an international online survey designed to better understand current practices and knowledge surrounding cellulose-based films showing signs of vinegar syndrome and naphthalene syndrome in order to determine gaps and potential areas for future research among organisations holding film collections. The findings of this survey suggest that confusion over aspects of film deterioration and the associated potential health effects appeared to be common among many respondents. It was determined that there was a distinct lack of knowledge surrounding the use of plasticisers such as triphenyl phosphate and the potential effects to health. However, it was found that the use of personal protective equipment and practices could be mitigating the potential dangers of handling highly deteriorated films. We suggest that further research into film plasticisers (such as monochloronaphthalene and organophosphorus esters) through testing work area air and dust samples may be beneficial in determining clearer safety parameters. [ABSTRACT FROM AUTHOR]

Substitution of diethyl and diphenyl benzylic phosphates, Alk-CH(Ar1)OP(O)(OR) 2 (R = Et, Ph; Alk = Me, Et, i -Pr; Ar1 = aryl), with the anions derived from Ar2CH 2 (Ph 2 CH 2 ,9 H -xanthene and fluorene) and n -BuLi at –15 °C was studied. For phosphates with Me as an Alk, diethyl phosphates produced Me-CH(Ar1)CH(Ar2) 2 (Ar1 = 4-halo-, 4-CN, 4-Me-, 2-Me, 2-Br-, 3-MeO-phenyl and 2-naphthyl). However, an unwanted substitution at the Et group competed with phosphates of Alk = Et- and i -Pr. Fortunately, the corresponding diphenyl phosphates cleanly underwent the desired substitution. Two enantioenriched phosphates, MeCH(Ph)OP(O)(OEt) 2 and EtCH(Ph)OP(O)(OPh) 2 , proceeded with complete inversion of the stereochemistry. Image 1 [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • In contrast to some opinions, derivatives of H 3 PO 4 do not initiate ROP of CL. • The traces of protic compounds in the catalyst act as initiators. • For the first time PCL with M n > 105 was obtained by CROP. • Controversy has been resolved: derivatives of H 3 PO 4 are only catalysts in CROP-AMM. Abstract Whenever Activated Monomer Mechanism (AMM) is involved in cationic ring-opening polymerization of cyclic esters, giving biodegradable polymers, catalysts and initiators are used. In some studies of AMM polymerization of ε -caprolactone (CL), without external initiator added, it was proposed that protonic catalysts are initiating themselves. We have shown by DOSY and other analytical methods for derivatives of phosphoric acid (claimed to act also as initiators) that these catalysts are not initiating polymerization and are separate from macromolecules. Traces of water are initiators. Understanding the role of catalysts in the bulk polymerization of CL allowed preparation of poly(ε -caprolactone) with M n up to 140,000, for the first time over 105 in AMM. [ABSTRACT FROM AUTHOR]

Phosphate flame retardants (PFRs) are ubiquitous chemicals in the indoor environment. Diphenyl phosphate (DPHP) is a major metabolite and a common biomarker of aryl-PFRs. Since it is used as a chemical additive and it is a common impurity of aryl-PFRs as well as a degradation product, its presence in indoor dust as an additional source of exposure should not be easily ruled out. In this study, DPHP (and TPHP) are measured in indoor dust in samples collected in Spain and in the Netherlands ( n = 80). Additionally, the presence of other emerging aryl-PFRs was monitored by target screening. TPHP and DPHP were present in all samples in the ranges 169–142,459 ng/g and 106–79,661 ng/g, respectively. DPHP concentrations were strongly correlated to the TPHP levels (r = 0.90, p < 0.01), suggesting that DPHP could be present as degradation product of TPHP or other aryl-PFRs. Estimated exposures for adults and toddlers in Spain to TPHP and DPHP via dust ingestion (country for which the number of samples was higher) were much lower than the estimated reference dose (US EPA) for TPHP. However, other routes of exposure may contribute to the overall internal exposure (diet, dermal contact with dust/consumer products and inhalation of indoor air). The estimated urinary DPHP levels for adults and toddlers in Spain (0.002–0.032 ng/mL) as a result of dust ingestion were low in comparison with the reported levels, indicating a low contribution of this source of contamination to the overall DPHP exposure. Other aryl-PFRs, namely cresyl diphenyl phosphate (CDP), resorcinol bis(diphenyl phosphate) (RDP), 2-ethylhexyl diphenyl phosphate (EDPHP), isodecyl diphenyl phosphate (IDP) and bisphenol A bis(diphenyl phosphate) (BDP), were all detected in indoor dust, however, with lower frequency. [ABSTRACT FROM AUTHOR]

Triphenyl phosphate (TPHP) is a commonly used organophosphate flame retardant and plasticizer with widespread human exposure. Data on health effects of TPHP are limited. Recent toxicological studies suggest TPHP may alter thyroid function. We used repeated measures to assess the temporal variability in urinary concentrations of the TPHP metabolite, diphenyl phosphate (DPHP), and to examine relationships between DPHP concentrations and thyroid hormones. We sampled 51 adults at months 1, 6, and 12 from 2010 to 2011. Urine samples were analyzed for DPHP. Serum samples were analyzed for free and total thyroxine (fT 4 , TT 4 ), total triiodothyronine (TT 3 ), and thyroid stimulating hormone (TSH). We assessed variability in DPHP using intraclass correlation coefficients (ICCs) and kappa statistics. We used linear mixed-effects models to examine associations between DPHP and thyroid hormones. DPHP was detected in 95% of urine samples. Mean DPHP concentrations were 43% higher in women than men. DPHP showed high within-subject variability (ICC range, 0.13–0.39; kappa range, 0.16–0.39). High versus low (≥ 2.65 vs. < 2.65 ng/mL) DPHP in all participants was associated with a 0.43 μg/dL (95% confidence interval: 0.15, 0.72) increase in mean TT 4 levels. In sex-stratified analyses, high versus low DPHP was associated with a 0.91 μg/dL (95% CI: 0.47, 1.36) increase in mean TT 4 in women. The association was attenuated in men (βeta = 0.19; 95% CI: − 0.15, 0.52). We found no significant associations between DPHP and fT 4 , TT 3 , or TSH. We found evidence that TPHP exposure may be associated with increased TT 4 levels, especially in women. [ABSTRACT FROM AUTHOR]

The use of triphenyl phosphate (TPhP) as a flame retardant or plasticizer has increased during the last decade, resulting in widespread human exposure without commensurate toxicity assessment. The main objectives of this study were to assess the in vitro effect of TPhP and its metabolite diphenyl phosphate (DPhP) on the adipogenic differentiation of 3T3-L1 cells, as well as glucose uptake and lipolysis in differentiated 3T3-L1 adipocytes. TPhP increased pre-adipocyte proliferation and subsequent adipogenic differentiation of 3T3-L1 cells, coinciding with increased transcription in the CEBP and PPARG pathway. Treatment of mature adipocytes with TPhP increased the basal- and insulin stimulated- uptake of the glucose analog 2-[N (-7-nitrobenz-2-oxa1, 3-diazol-4-yl) amino]-2-deoxy- d -glucose (2-NBDG). This effect was ablated by inhibition of PI3K, a member of the insulin signaling pathway. DPhP had no significant effect on cell proliferation and, compared to TPhP, a weaker effect on adipogenic differentiation and on 2-NBDG uptake. Both TPhP and DPhT significantly enhanced the isoproterenol-induced lipolysis, most likely by increasing the expression of lipolytic genes during and after differentiation. This study suggests that TPhP increases adipogenic differentiation, glucose uptake, and lipolysis in 3T3-L1 cells through endocrine and noradrenergic mechanisms. [ABSTRACT FROM AUTHOR]

[Display omitted] • The hepatocyte cytotoxicity of TPHP and its major metabolite DPHP were compared. • TPHP and DPHP exhibit different hepatocyte toxicity profiles. • TPHP is more potent than DPHP in inducing ER stress and insulin resistance in hepatocytes. • ER stress inhibitor 4-PBA partially restored TPHP induced insulin resistance. Triphenyl phosphate (TPHP) is a widely used flame retardant and plasticizer and has been detected extensively in environmental media, wildlife and human bodies. Several epidemiological and animal studies have revealed that TPHP exposure is positively associated with glucose homeostasis disruption and diabetes. However, the effects of TPHP on hepatic glucose homeostasis and the underlying mechanisms remain unclear. The present work aimed to investigate the cytotoxicity and glucose metabolism disruption of TPHP and its metabolite diphenyl phosphate (DPHP) within hepatocytes. The cell viability assay undertaken on human normal liver (L02) cells showed that TPHP exhibited more potent hepatotoxicity than DPHP. RNA sequencing (RNA-seq) data showed that TPHP and DPHP presented different modes of toxic action. Insulin resistance is one of the predominant toxicities for TPHP, but not for DPHP. The insulin-stimulated glucose uptake and glycogen synthesis were impaired by TPHP, while DPHP exhibited no significant impairment on these factors. TPHP exposure induced endoplasmic reticulum (ER) stress, and the ER stress antagonist 4-PBA restored the impairment of insulin-stimulated glucose uptake and glycogen synthesis induced by TPHP. TPHP could also induce liver ER stress and insulin resistance in mice. Taken together, the results suggested that TPHP induces more potent insulin resistance through ER stress than its metabolite DPHP. [ABSTRACT FROM AUTHOR]

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 10–14 h 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 24 h 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. [ABSTRACT FROM AUTHOR]

• MMIP nanocomposite with specific recognition ability was synthesized. • MMIP was used as an MSPE adsorbent to enrich urinary DPHP of college students. • DPHP levels showed a moderate reproducibility in first morning urine samples. • The high frequency of take-out food may lead to some OPEs exposure. Organophosphate esters (OPEs), known as novel alternative flame retardants, are a class of environmental endocrine disruptors. Long-term exposure to OPEs may bring a non-negligible health risk to human. Urinary OPE metabolites (mOPEs) are generally used as biomarkers to evaluate the internal exposure to OPEs. Diphenyl phosphate (DPHP), the main metabolite of aryl-OPEs, exhibited high detection rates and concentrations in urine samples. To establish a selective and simple analytical method for biomonitoring urinary DPHP, a specific magnetic molecular imprinted polymer (MMIP) was fabricated via a sol-gel method. Under optimum magnetic solid-phase extraction (MSPE) conditions, the resultant MMIP exhibited selective recognition ability, ideal adsorption capacity and good reusability on urinary DPHP enrichment. The developed MSPE method coupled with ultra-high performance liquid chromatography tandem mass spectrometry (U-HPLC-MS/MS) exhibited good precision and accuracy (spiked recoveries of 85.8%-109% with relative standard deviations (RSDs) ranged from 5.1%-13%), low detection limit of 0.035 ng/mL, and negligible matrix inhibition. Then we used this proposed method to detect urinary DPHP levels of recruited 30 college students and investigate the time variability and potential determinants. All urine samples revealed the presence of DPHP at a median concentration of 0.56 μg/g Creatinine (Cr). Moderate reproducibility of DPHP level was observed in first morning urine samples (ICC>0.40). Significant correlations were found between urinary DPHP levels and gender (β=0.72; 95% CI: 0.48∼0.96), sampling time (β=0.36; 95% CI: 0.08∼0.65) as well as the frequency for take-out food (β=0.45; 95% CI: 0.07∼0.74) (p < 0.05). Hence, a fast and sensitive MSPE-U-HPLC-MS/MS method was successfully built to quantify urinary DPHP. [ABSTRACT FROM AUTHOR]

Highlights: [•] We have developed a new method for the analysis of dialkyl and diaryl phosphates. [•] OASIS WAX, a weak anion exchange sorbent, had the best performance. [•] Derivatisation by methylation does not improve the analysis of DAPs by LC–MS/MS. [•] Diphenyl phosphate was the main DAP metabolite in urine. [•] GC–MS/MS is superior in terms of sensitivity for the chlorinated DAPs. [Copyright &y& Elsevier]

This study shows the synthesis, characterization, and evaluation of the effect of organophosphate antioxidant on the thermo-oxidative degradation of a mineral oil. The organophosphate was synthesized by nucleophilic substitution (S2) of hydrogenated cardanol. For this study, were employed thermogravimetry, derivative thermogravimetry, differential scanning calorimetry, and differential thermal analysis techniques. The results showed that organophosphate contributed for thermo-oxidative stability of mineral oil (initial decomposition temperature (IDT) mineral oil: 91.28 °C < IDT mineral oil + organophosphate (1%): 156.42 °C). The organophosphate obtained shows significant thermal stability when compared with other compound of the same class (diphenyl phosphate). [ABSTRACT FROM AUTHOR]

Abstract: Monodisperse molecularly imprinted polymers (MIPs) for diphenyl phosphate (DPP) and 1-naphthyl phosphate (1-NapP) have been prepared by a multi-step swelling and polymerization method using 4-vinylpyridine as a functional monomer, glycerol dimethacrylate as a crosslinker and cyclohexanol or 1-hexanol as a porogen. The retention and molecular-recognition properties of these MIPs for organophosphorus compounds were evaluated by HPLC using a mixture of phosphate buffer and acetonitrile as an eluent. In addition to shape recognition, hydrogen bonding and hydrophobic interactions could play an important role in the retention and molecular recognition of DPP and 1-NapP. Furthermore, the MIPs were applied to the separation of adenosine and adenosine phosphates (AMP, ADP and ATP). These phosphates were retained on the MIPs according to the number of phosphate groups in the molecule and were well separated from one another. Hydrogen bonding and hydrophobic interactions seemed to affect the retention and recognition of adenosine phosphates in low acetonitrile content, while hydrophilic interactions affected these properties in high acetonitrile content. Finally, the MIPs were applied to the trapping of phosphopeptides. The MIPs non-selectively trapped phosphopeptides, which have phosphorylated tyrosine, serine or threonine in the sequences, and successfully trapped four phosphopeptides in tryptic digests of bovine α-casein. [Copyright &y& Elsevier]

Background: The sorption of Y(III), La(III), Ce(III), U(VI) and Th(IV) ions with solvent impregnated resins using diphenylphosphate (DPP), and diphenylphosphinic acid (DPPA) as extractant and Amberlite XAD 16 and Amberlite XAD 2000 as a polymeric support has been studied. The impregnated resins containing various amounts of extractants (10/90, 20/80, 50/50, 60/40) have been prepared by a dry method. The effects of pH, types of extractant, extractant content, surface area of polymeric support and contact time have been investigated by batch method. Results: The impregnation for DPP on XAD-16 and XAD-2000 was 111 and 46% at 60/40 extractant/resin mass ratio, respectively. The impregnation of DPPA at all ratios on both resins was found constant and lower than DPP. The sorption percentage of studied metal ions was within 90-99% for DPP and DPPA on both resins after 20/80 extractant/resin mass ratio. Conclusions: The sorption of DPP on Amberlite XAD 16 and XAD 2000 resins is rather more than DPPA. It could be seen that 20/80 extractant/resin mass ratio is generally adequate for single metal analysis where 60/40 could be suitable for multi-metal analysis. [ABSTRACT FROM AUTHOR]

Abstract: Existing corrosion protection technologies for aluminium alloys utilising chromates are environmentally damaging and extremely toxic. This paper presents a preliminary investigation into rare earth diphenyl phosphates as new environmentally benign corrosion inhibitors. Full immersion weight loss experiments, cyclic potentiodynamic polarisation measurements and Raman spectroscopy were used in this study. Results show cerium diphenyl phosphate (Ce(dpp)3) acts as a cathodic inhibitor, decreasing cathodic current density and E corr by passivating cathodic intermetallic particles on the alloy surface. Mischmetal diphenyl phosphate (Mm(dpp)3) acts a mixed inhibitor, shifting E corr to more noble values, decreasing cathodic current density, increasing the breakdown potential and suppressing pitting. [Copyright &y& Elsevier]

[Display omitted] • Elevated DPHP and BDCIPP during mid-pregnancy increased ADHD risk in offspring. • Simultaneously decreasing joint exposure to OPEs and phthalates may reduce ADHD risk. • The link between prenatal DPHP and ADHD was stronger among girls than boys. • Suggestive modification by maternal paraoxonase1 Q192R genotype was present for DPHP. • DPHP-ADHD association was partly mediated via pregnancy maternal thyroid function. Organophosphate esters (OPEs) are a class of flame retardants in common use. OPEs can easily leach from materials, resulting in human exposure. Increasing concentrations have been reported in human populations over the past decade. Recent studies have linked prenatal OPE exposure to hyperactivity and attention problems in children. Such behaviors are often found among children with attention-deficit hyperactivity disorder (ADHD), however, no study has investigated OPEs in relation to clinically assessed ADHD. To evaluate prenatal exposure to OPEs as risk factors for clinically assessed ADHD using a case-cohort study nested within the Norwegian Mother, Father, and Child Cohort Study (MoBa). We included in the case group 295 ADHD cases obtained via linkage with the Norwegian Patient Registry, and the sub-cohort group 555 children sampled at baseline, irrespective of their ADHD case status. Prenatal concentrations of OPE metabolites were measured in maternal urine collected at 17 weeks of gestation, and included diphenyl phosphate (DPHP), di-n-butyl phosphate (DNBP), bis(2-butoxyethyl) hydrogen phosphate (BBOEP), and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP). We estimated risk ratios and the corresponding 95% confidence intervals [95% CI] using logistic regression, adjusting for season of urine collection, child sex, birth year, and maternal depression, education, and sum of urinary di(2-ethylhexyl) phthalate metabolites (∑DEHP) concentration during pregnancy. To assess the overall impact of simultaneously decreasing exposure to all chemical constituents of an OPE-phthalate mixture, quantile based g-computation was implemented. The mixture constituents included OPE and phthalate metabolites commonly detected in our study. In all models, we considered effect measure modification by child sex and polymorphisms in genes encoding paraoxonase 1 (PON1) and cytochrome P450 (P450) enzymes. Mediation analysis was conducted using thyroid function biomarkers estimated from maternal blood collected at 17 weeks of gestation. DPHP was detected in nearly all samples (97.2%), with a higher geometric mean among the case group (0.70 µg/L) as compared to the sub-cohort (0.52 µg/L). DNBP was commonly detected as well (93.8%), while BBOEP (52.9%) and BDCIPP (22.9%) were detected less frequently. A higher risk of ADHD was observed in children with greater than median exposure to DPHP during pregnancy (risk ratio: 1.38 [95% CI: 0.96, 1.99]), which was slightly higher among girls (2.04 [1.03, 4.02]) and children of mothers with PON1 Q192R genotype QR (1.69 [0.89, 3.19]) or PON1 Q192R genotype RR (4.59 [1.38, 15.29]). The relationship between DPHP and ADHD (total risk ratio: 1.34 [0.90, 2.02]) was partially mediated through total triiodothyronine to total thyroxine ratio (natural direct effect: 1.29 [0.87, 1.94]; natural indirect effect: 1.04 [1.00, 1.10]; 12.48% mediated). We also observed an elevated risk of ADHD in relation to BDCIPP detection during pregnancy (1.50 [0.98, 2.28]). We did not observe notable differences in ADHD by DNBP (0.88 [0.62, 1.26]) or BBOEP (1.03 [0.73, 1.46]) during pregnancy. Simultaneously decreasing all constituents of common-detect OPE-phthalate mixture, specifically DPHP, DNBP, and 6 phthalate metabolites, by a quartile resulted in an ADHD risk ratio of 0.68 [0.64, 0.72]. Prenatal exposure to DPHP and BDCIPP may increase the risk of ADHD. For DPHP, we observed potential modification by child sex and maternal PON1 Q192R genotype and partial mediation through maternal thyroid hormone imbalance at 17 weeks gestation. [ABSTRACT FROM AUTHOR]

Due to commercial uses and environmental degradation of aryl phosphate esters, diphenyl phosphate (DPhP) is frequently detected in environmental matrices and is thus of growing concern worldwide. However, information on potential adverse effects of chronic exposure to DPhP at environmentally realistic concentrations was lacking. Here, we investigated the effects of life cycle exposure to DPhP on zebrafish at environmentally relevant concentrations of 0.8, 3.9, or 35.6 μg/L and employed a dual-omics approach (metabolomics and transcriptomics) to characterize potential modes of action. Exposure to DPhP at 35.6 μg/L for 120 days resulted in significant reductions in body mass and length of male zebrafish, but did not cause those same effects to females. Predominant toxicological mechanisms, including inhibition of oxidative phosphorylation, down-regulation of fatty acid oxidation, and up-regulation of phosphatidylcholine degradation, were revealed by integrated dual-omics analysis and successfully linked to adverse outcomes. Activity of succinate dehydrogenase and protein content of carnitine O -palmitoyltransferase 1 were significantly decreased in livers of male fish exposed to DPhP, which further confirmed the proposed toxicological mechanisms. This study is the first to demonstrate that chronic, low-level exposure to DPhP can retard growth via inhibiting energy output in male zebrafish.

• Successful development of SPCE/ Au-NPs / TiO 2 / MIP sensor for DPP detection. • Characterizations were probed by EIS, DPV, CV, FTIR, AFM, SEM and EDS techniques. • Lower LOD (0.063 ng/mL) over a range of 0.1–24.3 ng/mL comparative to literatures. • Successful analysis of urine samples by MIP sensor and VE-tongue. • Chemometric approaches were used for classification and prediction. This research work deals with the diphenyl phosphate (DPP) detection in urine samples using a molecularly imprinted polymer (MIP) sensor and a voltammetric electronic tongue (VE-tongue). In this regard, gold nanoparticles (Au-NPs) and titanium dioxide (TiO 2) were first designed onto a screen-printed carbon electrode (SPCE). Then, the sensor was fabricated by bulk-polymerizing methacrylic acid in the presence of DPP molecules as template. To achieve a sensor with optimal performance, crucial experimental parameters were well optimized. This sensor exhibits good linearity over a range of 0.1–24.3 ng/mL (R2 = 0.98) as well as high sensitivity (0.141 μA/ng.mL−1) and low detection limit (LOD =0.063 ng/mL). Moreover, suitable stability and selectivity were achieved with reproducibility and repeatability reached a RSD of 2.3 and 3.02 %, respectively. For the DPP determination in urine samples from nail polish users, the sensor reveals good results in concordance with spectrophotometry as reference method with a (RSD ≤ 4%). Secondly, qualitative analysis was performed by a VE-tongue combined with chemometrics to classify urine samples of nail polish users. Partial least squares (PLS) method supplied prediction models achieved from the both systems data with a regression coefficient (R = 0.99). Accordingly, the MIP sensor and VE-tongue could be viable electrochemical tools for cosmetic applications. [ABSTRACT FROM AUTHOR]

Organophosphate esters (OPEs) are widely detected among U.S. pregnant women. OPEs, some of which are present in nail polish, have been associated with adverse reproductive health outcomes. More research is needed to investigate associations with OPEs and personal care products (PCP) use. Pregnant women (18–40 years) were recruited from two hospitals and five prenatal clinics in Northern Puerto Rico (n = 148 women) between 2011 and 2015. Concentrations of bis(2-chloroethyl) phosphate (BCEtP), bis(1-chloro-2-propyl) phosphate (BCPP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), di-n-butyl phosphate (DNBP), di-benzyl phosphate (DBzP), di-cresyl phosphate (DCP), DPHP, and 2,3,4,5-tetrabromobenzoic acid (TBBA) were measured twice during pregnancy. Participants completed questionnaires on PCP and household products (HP) use. Associations among products and metabolite concentrations (n = 296 observations) were assessed using linear mixed models. BCEtP, BCPP, BDCPP and DPHP were detected frequently (≥77%). Correlations among metabolites (0.16 ≤ r ≤ 0.35) and Intraclass correlation coefficients (ICCs) (0.03 ≤ ICC≤0.34) were weak-to-moderate. Suntan lotion was associated with a 110% increase in BDCPP. DPHP increased with perfume (51%) and nail polish (49%) use. BCPP increased 46% with pesticide use in home. Conclusion: Biomarkers of OPEs were often detected among pregnant women. Associations with PCP and HP use suggest OPEs may be used in such products, specifically in perfume and nail polish. Further investigation into these products is warranted. Image 1 • OPEs were widely detected among pregnant women. • Nail polish, perfume, and cosmetics use was associated with increased OPE metabolite concentrations. • Using pesticides in the home was associated with elevated OPE metabolite concentrations. • OPEs may be used in personal care and household products. [ABSTRACT FROM AUTHOR]

Organophosphate flame retardants (OPFRs) are commonly added to consumer products to reduce their flammability. Based on levels of OPFRs in indoor environments, human exposure is likely chronic and ubiquitous. Animal studies suggest that exposure to some OPFRs may result in adverse health impacts, particularly for Tris (1,3-dichloropropyl) phosphate (TDCPP); however, human data on the impacts of exposure to OPFRs are lacking. To design human studies, more information is needed on the stability of measured OPFRs in human samples over time. In this study, we sought to assess the degree of temporal variability of urinary TDCPP and triphenyl phosphate (TPP) metabolites throughout pregnancy in a cohort of women from central North Carolina. Eight pregnant women provided multiple urine samples: 3 during the 18th week of pregnancy, 1 during the 28th week, and 1 shortly after the child's birth. Bis (1,3-dichloropropyl) phosphate (BDCPP) and diphenyl phosphate (DPP), the respective metabolites of TDCPP and TPP, were measured in urine samples using liquid chromatography-tandem mass spectrometry. BDCPP and DPP were each detected in 38 of 39 urine samples and were not normally distributed. Geometric mean BDCPP and DPP concentrations were 1.3ng/mL (interquartile range (IQR): 0.8, 2.7ng/mL) and 1.9ng/mL (IQR: 0.9, 3.5ng/mL), respectively. BDCPP and DPP were moderately to strongly reliable over one week (intraclass correlation coefficient (ICC)=0.5; 95% confidence interval (CI): 0.4, 0.7 and ICC=0.7; 95% CI: 0.5, 0.8, respectively), and over the entire pregnancy (ICC=0.5 95% CI: 0.3, 0.7 and ICC=0.6; 95% CI: 0.4, 0.7, respectively). These data suggest that exposures to TDCPP and TPP are widespread and variable for pregnant women, and that a single measure of BDCPP or DPP, taken in the second trimester, likely captures information on the rank order of exposure throughout pregnancy., (Copyright © 2013 Elsevier Ltd. All rights reserved.)