Comparison of the toxicokinetics of daidzein and bisphenol A in pregnant and non-pregnant DA/Han rats

Potentially adverse human and environmental effects due to hormone mimicry of environmental estrogens are a matter of current concern. Environmental estrogens belong to the socalled endocrine active compounds (EAC) and may alter signalling processes of the endocrine system leading to a broad range of effects during fetal and postnatal development, puberty, adulthood, and aging. A number of synthetic chemicals as well as several plant-derived compounds, socalled phytoestrogens, are known to have weak estrogenic activity. The present study is part of the risk assessment of the weak environmental estrogens daidzein and bisphenol A. The isoflavone daidzein is an important phytoestrogen with respect to dietary exposure (soy beans and soy products) whereas bisphenol A is an industrial chemical that occurs at much lower concentrations as a contaminant in food. The toxicokinetics of these compounds in female pregnant and non-pregnant DA/Han rats after single intravenous application were compared by the use of the Mann-Whitney- U-statistic. --Bisphenol A,daidzein,xenoestrogens,phytoestrogens,endocrine active compounds,Mann-Whitney-U-test

Metabolic profile, bioavailability and toxicokinetics of zearalenone-14-glucoside in rats after oral and intravenous administration by liquid chromatography high-resolution mass spectrometry and tandem mass spectrometry

Zearalenone-14-glucoside (ZEN-14G), a key modified mycotoxin, has attracted a great deal of attention due to the possible conversion to its free form of zearalenone (ZEN) exerting toxicity. In this study, the toxicokinetics of ZEN-14G were investigated in rats after oral and intravenous administration. The plasma concentrations of ZEN-14G and its major five metabolites were quantified using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The data were analyzed via non-compartmental analysis using software WinNonlin 6.3. The results indicated that ZEN-14G was rapidly hydrolyzed into ZEN in vivo. In addition, the major parameters of ZEN-14G following intravenous administration were: area under the plasma concentration-time curve (AUC), 1.80 h.ng/mL; the apparent volume of distribution (V-Z), 7.25 L/kg; and total body clearance (CL), 5.02 mL/h/kg, respectively. After oral administration, the typical parameters were: AUC, 0.16 h.ng/mL; V-Z, 6.24 mL/kg; and CL, 4.50 mL/h/kg, respectively. The absolute oral bioavailability of ZEN-14G in rats was about 9%, since low levels of ZEN-14G were detected in plasma, which might be attributed to its extensive metabolism. Therefore, liquid chromatography high-resolution mass spectrometry (LC-HRMS) was adopted to clarify the metabolic profile of ZEN-14G in rats' plasma. As a result, eight metabolites were identified in which ZEN-14-glucuronic acid (ZEN-14GlcA) had a large yield from the first time-point and continued accumulating after oral administration, indicating that ZEN-14-glucuronic acid could serve a potential biomarker of ZEN-14G. The obtained outcomes would prompt the accurate safety evaluation of ZEN-14G

Toxicokinetics and bioconcentration of polycyclic aromatic hydrocarbons in freshwater isopods

A novel method based on a first-order two-compartment model was used to determine the bioconcentration and toxicokinetic rate constants of six different polycyclic aromatic hydrocarbons (PAHs) in the freshwater isopod Asellus aquaticus, a common species in most European freshwater systems. Numerical integration and iterative parameter estimation techniques were applied to account for time-varying aqueous exposure concentrations. All PAHs exhibited a rapid uptake. Monophasic elimination patterns were observed for benzo[e]pyrene and benzo[a]-pyrene (biological half-life

A geometric characterization of cc-optimal designs for heteroscedastic regression

We consider the common nonlinear regression model where the variance, as well as the mean, is a parametric function of the explanatory variables. The $c$-optimal design problem is investigated in the case when the parameters of both the mean and the variance function are of interest. A geometric characterization of $c$-optimal designs in this context is presented, which generalizes the classical result of Elfving [Ann. Math. Statist. 23 (1952) 255--262] for $c$-optimal designs. As in Elfving's famous characterization, $c$-optimal designs can be described as representations of boundary points of a convex set. However, in the case where there appear parameters of interest in the variance, the structure of the Elfving set is different. Roughly speaking, the Elfving set corresponding to a heteroscedastic regression model is the convex hull of a set of ellipsoids induced by the underlying model and indexed by the design space. The $c$-optimal designs are characterized as representations of the points where the line in direction of the vector $c$ intersects the boundary of the new Elfving set. The theory is illustrated in several examples including pharmacokinetic models with random effects.Comment: Published in at http://dx.doi.org/10.1214/09-AOS708 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Risks for public health related to the presence of tetrodotoxin (TTX) and TTX analogues in marine bivalves and gastropods

Peer reviewedPublisher PD

Comparison of Blood and Brain Mercury Levels in Infant Monkeys Exposed to Methylmercury or Vaccines Containing Thimerosal

Thimerosal is a preservative that has been used in manufacturing vaccines since the 1930s. Reports have indicated that infants can receive ethylmercury (in the form of thimerosal) at or above the U.S. Environmental Protection Agency guidelines for methylmercury exposure, depending on the exact vaccinations, schedule, and size of the infant. In this study we compared the systemic disposition and brain distribution of total and inorganic mercury in infant monkeys after thimerosal exposure with those exposed to MeHg. Monkeys were exposed to MeHg (via oral gavage) or vaccines containing thimerosal (via intramuscular injection) at birth and 1, 2, and 3 weeks of age. Total blood Hg levels were determined 2, 4, and 7 days after each exposure. Total and inorganic brain Hg levels were assessed 2, 4, 7, or 28 days after the last exposure. The initial and terminal half-life of Hg in blood after thimerosal exposure was 2.1 and 8.6 days, respectively, which are significantly shorter than the elimination half-life of Hg after MeHg exposure at 21.5 days. Brain concentrations of total Hg were significantly lower by approximately 3-fold for the thimerosal-exposed monkeys when compared with the MeHg infants, whereas the average brain-to-blood concentration ratio was slightly higher for the thimerosal-exposed monkeys (3.5 ± 0.5 vs. 2.5 ± 0.3). A higher percentage of the total Hg in the brain was in the form of inorganic Hg for the thimerosal-exposed monkeys (34% vs. 7%). The results indicate that MeHg is not a suitable reference for risk assessment from exposure to thimerosal-derived Hg. Knowledge of the toxicokinetics and developmental toxicity of thimerosal is needed to afford a meaningful assessment of the developmental effects of thimerosal-containing vaccines

Safety assessment of the substance phosphorous acid, mixed 2,4-bis(1,1-dimethylpropyl)phenyl and 4-(1,1-dimethylpropyl)phenyl triesters for use in food contact materials

Publisher PD

An assessment of organic solvent based equilibrium partitioning methods for predicting the bioconcentration behavior of perfluorinated sulfonic acids, carboxylic acids, and sulfonamides

SPARC, KOWWIN, and ALOGPS octanol-water partitioning (log K~ow~) and distribution (log D) constants were calculated for all C~1~ through C~8~ and the straight chain C~9~ through C~15~ perfluoroalkyl sulfonic acids (PFSAs) and carboxylic acids (PFCAs). Application of five established models for estimating bioconcentration factors (BCFs) were applied to the PFSA and PFCA log K~ow~ and log D data and compared to available field and laboratory BCF data. Wide variability was observed between the methods for estimating log K~ow~ and log D values, ranging up to several log units for particular congeners, and which was further compounded by additional variability introduced by the different BCF equations applied. With the exception of n-perfluorooctanecarboxylic acid (n-PFOA), whose experimental BCF was poorly modeled by all approaches, the experimental BCF values of the other PFSA and PFCA congeners were reasonably approximated by the ALOGPS log P values in combination with any of the five log K~ow~ based BCF equations. The SPARC and KOWWIN log K~ow~ and log D values provided generally less accurate BCF estimates regardless of the BCF equation applied. However, the SPARC K~ow~ values did provide BCF estimates for PFSA congeners with errors <0.3 log units using any of the five BCF equations. Model lipophilic and proteinophilic solvent based distribution constant calculations for the PFSA and PFCA congeners with experimental BCFs exhibited similar relationships with their corresponding BCF values. For longer chain PFCA and PFSA congeners, increasing hydrophobicity of the perfluoroalkyl chain appears to be driving corresponding increases in BCF values. Perfluorooalkyl sulfonamides are expected to display similar chain length and branching pattern influences on BCFs, but no experimental data are currently available upon which to validate the estimated values which range widely between the various approaches by up to 10 log units. The amidic proton acidity on primary and secondary perfluoroalkyl sulfonamides will play a significant role in the partitioning of these compounds with both abiotic and biotic organic matter, and will need to be taken into account when assessing their environmental and biological fate