Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A

Bisphenol A (BPA) is one of the highest-volume chemicals produced worldwide, and human exposure to BPA is thought to be ubiquitous. Thus, there are concerns that the amount of BPA to which humans are exposed may cause adverse health effects. We examined many possibilities for why biomonitoring and toxicokinetic studies could come to seemingly conflicting conclusions. More than 80 published human biomonitoring studies that measured BPA concentrations in human tissues, urine, blood, and other fluids, along with two toxicokinetic studies of human BPA metabolism were examined. Unconjugated BPA was routinely detected in blood (in the nanograms per milliliter range), and conjugated BPA was routinely detected in the vast majority of urine samples (also in the nanograms per milliliter range). In stark contrast, toxicokinetic studies proposed that humans are not internally exposed to BPA. Available data from biomonitoring studies clearly indicate that the general population is exposed to BPA and is at risk from internal exposure to unconjugated BPA. The two toxicokinetic studies that suggested human BPA exposure is negligible have significant deficiencies, are directly contradicted by hypothesis-driven studies, and are therefore not reliable for risk assessment purposes.Bisfenol A (BPA) é um dos produtos químicos mais produzido em todo o mundo, e a exposição humana a ele é considerada onipresente. Assim, há preocupações de que a quantidade de BPA para o qual os seres humanos estão expostos podem causar efeitos adversos à saúde. Nós examinamos muitas possibilidades sobre o porquê estudos de biomonitorização e toxicocinética podem chegar a conclusões aparentemente conflitantes. Mais de 80 estudos publicados de biomonitorização humana que mediram a concentração de BPA em tecidos humanos, urina, sangue e outros fluidos, juntamente com dois estudos de toxicocinética do metabolismo humano BPA foram examinados. BPA não conjugado foi detectado no sangue (nonanogramas por mililitro gama), e BPA conjugado foi detectado na grande maioria das amostras de urina. Em contraste, estudos de toxico-cinética propuseram que os seres humanos não são internamente expostos ao BPA. Dados disponíveis de estudos de biomonitorização indicam que a população em geral está exposta ao BPA e em risco de exposição interna ao BPA não conjugado. Os dois estudos de toxicocinética, que sugeriram a exposição humana ao BPA é insignificante, têm deficiências significativas e estão diretamente refutados por outros estudos e, portanto não são confiáveis para fins de avaliação de risco

A stochastic flow rule for granular materials

There have been many attempts to derive continuum models for dense granular flow, but a general theory is still lacking. Here, we start with Mohr-Coulomb plasticity for quasi-2D granular materials to calculate (average) stresses and slip planes, but we propose a "stochastic flow rule" (SFR) to replace the principle of coaxiality in classical plasticity. The SFR takes into account two crucial features of granular materials - discreteness and randomness - via diffusing "spots" of local fluidization, which act as carriers of plasticity. We postulate that spots perform random walks biased along slip-lines with a drift direction determined by the stress imbalance upon a local switch from static to dynamic friction. In the continuum limit (based on a Fokker-Planck equation for the spot concentration), this simple model is able to predict a variety of granular flow profiles in flat-bottom silos, annular Couette cells, flowing heaps, and plate-dragging experiments -- with essentially no fitting parameters -- although it is only expected to function where material is at incipient failure and slip-lines are inadmissible. For special cases of admissible slip-lines, such as plate dragging under a heavy load or flow down an inclined plane, we postulate a transition to rate-dependent Bagnold rheology, where flow occurs by sliding shear planes. With different yield criteria, the SFR provides a general framework for multiscale modeling of plasticity in amorphous materials, cycling between continuum limit-state stress calculations, meso-scale spot random walks, and microscopic particle relaxation

Wide shear zones and the spot model: Implications from the split-bottom geometry

The spot model has been developed by Bazant and co-workers to describe quasistatic granular flows. It assumes that granular flow is caused by the opposing flow of so-called spots of excess free volume, with spots moving along the slip lines of Mohr-Coulomb plasticity. The model is two-dimensional and has been successfully applied to a number of different geometries. In this paper we investigate whether the spot model in its simplest form can describe the wide shear zones observed in experiments and simulations of a Couette cell with split bottom. We give a general argument that is independent of the particular description of the stresses, but which shows that the present formulation of the spot model in which diffusion and drift terms are postulated to balance on length scales of order of the spot diameter, i.e. of order 3-5 grain diameters, is difficult to reconcile with the observed wide shear zones. We also discuss the implications for the spot model of co-axiality of the stress and strain rate tensors found in these wide shear flows, and point to possible extensions of the model that might allow one to account for the existence of wide shear zones.Comment: 6 pages, 6 figures, to be published in EPJ

Toksikokinetika prometrina u mozgu miševa

Prometryne is a methylthio-s-triazine herbicide. Signifi cant trace amounts are found in the environment, mainly in water, soil, and food plants. The aim of this study was to establish brain and blood prometryne levels after single oral dose (1 g kg-1) in adult male and female mice. Prometryne was measured using the GC/MS assay at 1, 2, 4, 8, and 24 h after prometryne administration. Peak brain and blood prometryne values were observed 1 h after administration and they decreased in a time-dependent manner. Male mice had consistently higher brain and blood prometryne levels than female mice. The observed prometryne kinetics was similar to that reported for the structurally related herbicide atrazine.Prometrin je metiltio-s-triazinski herbicid. Značajne količine prometrina zaostaju u tragovima u okolišu, poglavito u vodi, tlu i biljkama koje rabimo za prehranu. Cilj je rada izmjeriti količinu prometrina koja se apsorbira u mozgu i krvi nakon primijenjene akutne oralne doze (1 g kg-1 tjelesne mase) u odraslih miševa obaju spolova. Razine prometrina u mozgu i krvi izmjerene su GC/MS-om tijekom 1., 2., 4., 8. i 24. sata nakon izlaganja. Utvrđeno je da je udio prometrina koji se zadržava u živčanom tkivu relativno nizak ali detektabilan u odnosu na koncentraciju u krvi i koncentraciju primijenjene doze. Najviše koncentracije u krvi i maseni udjeli u mozgu zabilježeni su tijekom 1. sata nakon izlaganja, a s vremenom izmjerene vrijednosti značajno opadaju. Uočena je značajna razlika između mužjaka i ženki pri čemu mužjaci imaju značajno više razine prometrina u mozgu i krvi nego ženke. Opisana toksikokinetika prometrina pokazuje sličnosti s otprije opisanom i poznatom toksikokinetikom strukturalno sličnog herbicida atrazina

Non-local rheology in dense granular flows -- Revisiting the concept of fluidity

Granular materials belong to the class of amorphous athermal systems, like foams, emulsion or suspension they can resist shear like a solid, but flow like a liquid under a sufficiently large applied shear stress. They exhibit a dynamical phase transition between static and flowing states, as for phase transitions of thermodynamic systems, this rigidity transition exhibits a diverging length scales quantifying the degree of cooperatively. Several experiments have shown that the rheology of granular materials and emulsion is non-local, namely that the stress at a given location does not depend only on the shear rate at this location but also on the degree of mobility in the surrounding region. Several constitutive relations have recently been proposed and tested successfully against numerical and experimental results. Here we use discrete elements simulation of 2D shear flows to shed light on the dynamical mechanism underlying non-locality in dense granular flows

Effect of Acinetobacter sp on Metalaxyl Degradation and Metabolite Profile of Potato Seedlings (Solanum tuberosum L.) Alpha Variety

One of the most serious diseases in potato cultivars is caused by the pathogen Phytophthora infestans, which affects leaves, stems and tubers. Metalaxyl is a fungicide that protects potato plants from Phytophthora infestans. In Mexico, farmers apply metalaxyl 35 times during the cycle of potato production and the last application is typically 15 days before harvest. There are no records related to the presence of metalaxyl in potato tubers in Mexico. In the present study, we evaluated the effect of Acinetobacter sp on metalaxyl degradation in potato seedlings. The effect of bacteria and metalaxyl on the growth of potato seedlings was also evaluated. A metabolite profile analysis was conducted to determine potential molecular biomarkers produced by potato seedlings in the presence of Acinetobacter sp and metalaxyl. Metalaxyl did not affect the growth of potato seedlings. However, Acinetobacter sp strongly affected the growth of inoculated seedlings, as confirmed by plant length and plant fresh weights which were lower in inoculated potato seedlings (40% and 27%, respectively) compared to the controls. Acinetobacter sp also affected root formation. Inoculated potato seedlings showed a decrease in root formation compared to the controls. LC-MS/MS analysis of metalaxyl residues in potato seedlings suggests that Acinetobacter sp did not degrade metalaxyl. GC–TOF–MS platform was used in metabolic profiling studies. Statistical data analysis and metabolic pathway analysis allowed suggesting the alteration of metabolic pathways by both Acinetobacter sp infection and metalaxyl treatment. Several hundred metabolites were detected, 137 metabolites were identified and 15 metabolic markers were suggested based on statistical change significance found with PLS-DA analysis. These results are important for better understanding the interactions of putative endophytic bacteria and pesticides on plants and their possible effects on plant metabolism

Extended kinetic theory applied to inclined granular flows: role of boundaries

We compare the predictions of extended kinetic theory (EKT), where the roles of surface friction and correlation in fluctuation velocities are taken into account, with discrete element simulations of steady, fully-developed, inclined flows of identical spheres over bumpy bases, in the presence and absence of flat, frictional sidewalls. We show that the constitutive relation for the pressure of EKT must be modified in the proximity of the boundary, because of the influence of excluded volume and shielding associated with collisions of particles with the boundary itself. We also note that currently available boundary conditions for flows over bumpy planes in kinetic theory underestimate the energy dissipation. These two observations explain the lack of agreement of EKT with the simulations, in terms of the maximum angles of inclination for which steady, fully-developed flows are possible. That is, for some high angles of inclination, EKT does not have solutions, while steady flows are predicted in DEM. However, whenever a solution to the system of differential equations of EKT does exist, the predicted distributions of velocity, solid volume fraction and granular temperature satisfactorily match the numerical measurements. The incompressible, algebraic approximation of EKT, which ignores the conduction of energy in the energy balance, admits solutions for a wider range of angles of inclination, as in the simulations, but fails to reproduce the quantitative and qualitative behaviour of solid volume fraction and granular temperature in the two conductive layers at the top and bottom of the flow. When frictional sidewalls are added to the domain, we show that the spanwise ratio of shear stress to pressure is linearly distributed in the dense core region of the flow, confirming that the sidewalls exert, on average, a Coulomb-like resistance to the flow with an effective friction coefficient which is less than half the actual particle-wall friction

A round robin approach to the analysis of bisphenol a (BPA) in human blood samples

BACKGROUND: Human exposure to bisphenol A (BPA) is ubiquitous, yet there are concerns about whether BPA can be measured in human blood. This Round Robin was designed to address this concern through three goals: 1) to identify collection materials, reagents and detection apparatuses that do not contribute BPA to serum; 2) to identify sensitive and precise methods to accurately measure unconjugated BPA (uBPA) and BPA-glucuronide (BPA-G), a metabolite, in serum; and 3) to evaluate whether inadvertent hydrolysis of BPA-G occurs during sample handling and processing. METHODS: Four laboratories participated in this Round Robin. Laboratories screened materials to identify BPA contamination in collection and analysis materials. Serum was spiked with concentrations of uBPA and/or BPA-G ranging from 0.09-19.5 (uBPA) and 0.5-32 (BPA-G) ng/mL. Additional samples were preserved unspiked as ‘environmental’ samples. Blinded samples were provided to laboratories that used LC/MSMS to simultaneously quantify uBPA and BPA-G. To determine whether inadvertent hydrolysis of BPA metabolites occurred, samples spiked with only BPA-G were analyzed for the presence of uBPA. Finally, three laboratories compared direct and indirect methods of quantifying BPA-G. RESULTS: We identified collection materials and reagents that did not introduce BPA contamination. In the blinded spiked sample analysis, all laboratories were able to distinguish low from high values of uBPA and BPA-G, for the whole spiked sample range and for those samples spiked with the three lowest concentrations (0.5-3.1 ng/ml). By completion of the Round Robin, three laboratories had verified methods for the analysis of uBPA and two verified for the analysis of BPA-G (verification determined by: 4 of 5 samples within 20% of spiked concentrations). In the analysis of BPA-G only spiked samples, all laboratories reported BPA-G was the majority of BPA detected (92.2 – 100%). Finally, laboratories were more likely to be verified using direct methods than indirect ones using enzymatic hydrolysis. CONCLUSIONS: Sensitive and accurate methods for the direct quantification of uBPA and BPA-G were developed in multiple laboratories and can be used for the analysis of human serum samples. BPA contamination can be controlled during sample collection and inadvertent hydrolysis of BPA conjugates can be avoided during sample handling