Exposure characteristics and cumulative risk assessment of bisphenol A and its substitutes: the Taiwan environmental survey for toxicants 2013

IntroductionEver since the use of bisphenol A (BPA) has been restricted, concerns have been raised regarding the use of its substitutes, such as bisphenol S (BPS) and bisphenol F (BPF). Meanwhile, the EU European Food Safety Authority (EFSA) issued the new tolerable daily intake (TDI) after the latest re-risk assessment for BPA, which enforced the need for cumulative risk assessment in the population. This study was conducted to identify BPA and its substitute’s exposure characteristics of the general Taiwanese population and estimate the cumulative risk of bisphenol exposure.MethodsUrine samples (N = 366 [adult, 271; minor, 95]) were collected from individuals who participated in the Taiwan Environmental Survey for Toxicants 2013. The samples were analyzed for BPA, BPS, and BPF through ultraperformance liquid chromatography–tandem mass spectrometry. Daily intake (DI) levels were calculated for each bisphenol. Hazard quotients (HQs) were calculated with the consideration of tolerable DI and a reference dose. Additionally, hazard index (HI; sum of HQs for each bisphenol) values were calculated.ResultsOur study found that the median level of BPA was significantly higher in adults (9.63 μg/g creatinine) than in minors (6.63 μg/g creatinine) (p < 0.001). The DI of BPS was higher in female (0.69 ng/kg/day) than in male (0.49 ng/kg/day); however, the DIs of BPF and BPS were higher in boys (1.15 and 0.26 ng/kg/day, respectively) than in girls (0.57 and 0.20 ng/kg/day, respectively). Most HI values exceeded 1 (99% of the participants) after EFSA re-establish the TDI of BPA.DiscussionOur study revealed that the exposure profiles and risk of BPA and its substitute in Taiwanese varied by age and sex. Additionally, the exposure risk of BPA was deemed unacceptable in Taiwan according to new EFSA regulations, and food contamination could be the possible source of exposure. We suggest that the risk of exposure to BPA and its substitutes in most human biomonitoring studies should be reassessed based on new scientific evidence

The cholesterol-hydroxyecdysone-vitellogenin pathway is involved in the longevity of trophocytes and oenocytes of queen honey bees (Apis mellifera)

International audienceAbstractTrophocytes and oenocytes in the abdomen of honey bees do not divide after eclosion; however, trophocytes and oenocytes of queen bees have a longer lifespan and maintain better cellular function than those of worker bees. To explore this phenomenon, we assayed the molecules involved in the cholesterol-hydroxyecdysone-vitellogenin (Vg) pathway in the trophocytes and oenocytes of young and old worker and queen bees. The results showed that Vg and cholesterol levels in hemolymph and cholesterol levels, 20-hydroxyecdysone (20E) levels, and the messenger RNA levels of cytochrome P450 314A1 20-hydroxylase (Cyp314A1), ecdysone receptor isoform A (EcR-A), ecdysone receptor isoform B1 (EcR-B1), ultraspiracle (USP), ecdysone-induced protein 74 (E74), ecdysone-induced protein 75 (E75), broad-complex (BR-C), Vg, and Vg receptor (VgR) in trophocytes and oenocytes were increased in queen bees compared with worker bees. These findings indicated that queen bees have higher expression of molecules in the cholesterol-hydroxyecdysone-Vg pathway than worker bees

Exposure and risk assessment of urinary trans, trans-Muconic acid in school-age children in the vicinity of a petrochemical complex in Central Taiwan

School-age children living near large petrochemical factories may be at high risk of exposure to benzene released during manufacturing processes. We aimed to investigate the urinary concentrations of trans, trans-muconic acid (t,t-MA) in school-age children living near a petrochemical complex and to estimate their cumulative risk of benzene exposure. We examined an established cohort (Taiwan Petrochemical Complex Cohort for Children, TPE3C) of school-age children (aged 6–13 years) who lived near large petrochemical factories in central Taiwan between October 2013 and September 2014. The cohort comprised 297 children from five elementary schools, namely S.-C. Branch (n = 63, school A, ~0.9 km), F.-A. (n = 51, school B, ~2.7 km), C.-T. (n = 63, school C, ~5.5 km), M.-L. (n = 54, school D, ~6.9 km), and L.-F. (n = 66, school E, ~8.6 km). We analyzed the urinary t,t-MA levels of each participant and estimated their daily intake of benzene. We also performed multiple regression analysis to investigate potential risk factors for a high urinary t,t-MA level in the study cohort. The median urinary t,t-MA levels and median estimated benzene daily intake of the children from each school were as follows: school A, 64.07 ng/mL, 11.13 μg/kg/day; school B, 61.01 ng/mL, 15.32 μg/kg/day; school C, 59.38 ng/mL, 14.81 μg/kg/day; school D, 42.35 ng/mL, 11.67 μg/kg/day; school E, undetected, 0.14 μg/kg/day. The distance between a school and a petrochemical complex (greater distance: β = −0.26, 95% confidence interval [CI] = −0.52 to 0.00, p = 0.053), and the age of the children (older age: β = −3.44, 95% CI = −5.90 to −1.46, p < 0.001) were identified as potential risk factors. After confounders were adjusted for, the creatinine adjusted urinary t,t-MA levels of the school-age children tended to be lower when the distance between their school and a petrochemical complex was greater

Inhibition of Serine Protease Activity Protects Against High Fat Diet-Induced Inflammation and Insulin Resistance.

Recent evidence suggests that enhanced protease-mediated inflammation may promote insulin resistance and result in diabetes. This study tested the hypothesis that serine protease plays a pivotal role in type 2 diabetes, and inhibition of serine protease activity prevents hyperglycemia in diabetic animals by modulating insulin signaling pathway. We conducted a single-center, cross-sectional study with 30 healthy controls and 57 patients with type 2 diabetes to compare plasma protease activities and inflammation marker between groups. Correlations of plasma total and serine protease activities with variables were calculated. In an in-vivo study, LDLR-/- mice were divided into normal chow diet, high-fat diet (HFD), and HFD with selective serine protease inhibition groups to examine the differences of obesity, blood glucose level, insulin resistance and serine protease activity among groups. Compared with controls, diabetic patients had significantly increased plasma total protease, serine protease activities, and also elevated inflammatory cytokines. Plasma serine protease activity was positively correlated with body mass index, hemoglobin A1c, homeostasis model assessment-insulin resistance index (HOMA-IR), tumor necrosis factor-α, and negatively with adiponectin concentration. In the animal study, administration of HFD progressively increased body weight, fasting glucose level, HOMA-IR, and upregulated serine protease activity. Furthermore, in-vivo serine protease inhibition significantly suppressed systemic inflammation, reduced fasting glucose level, and improved insulin resistance, and these effects probably mediated by modulating insulin receptor and cytokine expression in visceral adipose tissue. Our findings support the serine protease may play an important role in type 2 diabetes and suggest a rationale for a therapeutic strategy targeting serine protease for clinical prevention of type 2 diabetes

The Arabidopsis Malectin-Like/LRR-RLK IOS1 is Critical for BAK1-Dependent and BAK1-Independent Pattern-Triggered Immunity

Plasma membrane-localized pattern recognition receptors (PRRs) such as FLAGELLIN SENSING2 (FLS2), EF-TU RECEPTOR (EFR) and CHITIN ELICITOR RECEPTOR KINASE 1 (CERK1) recognize microbe-associated molecular patterns (MAMPs) to activate pattern-triggered immunity (PTI). A reverse genetics approach on genes responsive to the priming agent beta-aminobutyric acid (BABA) revealed IMPAIRED OOMYCETE SUSCEPTIBILITY1 (IOS1) as a critical PTI player. Arabidopsis thaliana ios1 mutants were hyper-susceptible to Pseudomonas syringae bacteria. Accordingly, ios1 mutants showed defective PTI responses, notably delayed up-regulation of the PTI-marker gene FLG22-INDUCED RECEPTOR-LIKE KINASE1 (FRK1), reduced callose deposition and mitogen-activated protein kinase activation upon MAMP treatment. Moreover, Arabidopsis lines over-expressing IOS1 were more resistant to bacteria and showed a primed PTI response. In vitro pull-down, bimolecular fluorescence complementation, co-immunoprecipitation, and mass spectrometry analyses supported the existence of complexes between the membrane-localized IOS1 and BRASSINOSTEROID INSENSITIVE1-ASSOCIATED KINASE1 (BAK1)-dependent PRRs FLS2 and EFR, as well as with the BAK1-independent PRR CERK1. IOS1 also associated with BAK1 in a ligand-independent manner, and positively regulated FLS2-BAK1 complex formation upon MAMP treatment. In addition, IOS1 was critical for chitin-mediated PTI. Finally, ios1 mutants were defective in BABA-induced resistance and priming. This work reveals IOS1 as a novel regulatory protein of FLS2-, EFR- and CERK1-mediated signaling pathways that primes PTI activation