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

Estimation of the Mean AUC of the Xenoestrogens Daidzein, Bisphenol A, and p-tert-Octylphenol

Potentially adverse human and environmental effects due to hormone mimicry of environmental estrogens are a matter of current concern. Environmental estrogens belong to the so-called endocrine active compounds (EAC), which alter signalling processes of the endocrine system leading to a broad range of effects during foetal and postnatal development, puberty, adulthood, and aging. A number of synthetic chemicals as well as several plant-derived compounds, so-called phytoestrogens, are known to have weak estrogenic activity. The present study is part of the risk assessment of the weak environmental estrogens daidzein, p-tert-octylphenol, and bisphenol A. The isoflavone daidzein is an important phytoestrogen with respect to dietary exposure (soy beans and soy products). p-tert-Octylphenol and bisphenol A are industrial chemicals. The toxicokinetics and the bioavailability of these three substances in female DA/Han rats after oral and single intravenous application were investigated by the use of population models accounting for the differences in the individual metabolism. Furthermore, populations of pregnant and non-pregnant rats are compared

Novi aspekti u klasifikaciji kancerogena

The existing systems of classification of carcinogens should include a distinction between genotoxic and non-genotoxic chemicals. For non-genotoxic chemicals, permissible exposure levels can be derived at which no relevant human cancer risks are anticipated. While genotoxic carcinogens can induce chromosomal effects without mutagenic action, non-DNA-reactive genotoxins affecting topoisomerase or the spindle, or those having an exclusively aneugenic effect can be carcinogenic only at high, toxic doses. Specific mechanisms of clastogenicity and processes of carcinogenesis based on reactive oxygen have practical thresholds. Since reactive oxygen species (ROS) are generally genotoxic, the question is whether chemicals that increase ROS production will add to endogenously produced background levels and lead to nonlinear dose-effect relationships. Taking into account the presence of endogenous carcinogens, it is now becoming evident that carcinogenic risk extrapolation to low doses must be considered according to the mode of action.U postojećem sistemu klasifikacije kancerogenih tvari utvrđena je razlika između genotoksičnih i negenotoksičnih kemikalija. Za negenotoksične kemikallije mogu se izvesti pretpostavljeni stupnjevi izlaganja kod kojih ne postoji značajan rizik od pojave raka kod ljudi. Za genotoksične kancerogene mogući su na primjer inducirani kromosomski efekti bez početka procesa mutageneze, dok genotoksični toksini koji se ne vežu za DNA-molekulu, a djeluju na topoizomere ili diobeno vreteno ili su aneugeni, izazivaju kancerogene efekte jedino u visokim, toksičnim dozama. Za specifične mehanizme klastrogenog djelovanja i procesa kancerogeneze koji se baziraju na reaktivnom kisiku postoji prag početka procesa. Kako su vrste kemikalija reaktivne na kisik (ROS) u načelu genotoksične, pojavljuju se pitanja da li kemikalije koje povećavaju produkciju ROS-vrsta treba pridodati endogenim kancerogenima pozadinskog stupnja koji uzrokuju nelinearni odnos doze i učinka. Uzimajući u obzir rasprave o prisutnosti endogenih kancerogena, sada postaje jasno da se kancerogeni rizik od niskih doza mora uzeti u obzir sukladno načinu njihova djelovanja

Эпидемиологические исследования в сексологии

Представлены результаты эпидемиологического исследования, позволившие автору на примере обследования 1000 человек популяции из западного региона Украины сформулировать основные закономерности изменения отношения к браку и сексуального поведения мужчин и женщин в современном обществе.The findings of epidemiological study, which allowed the author to formulate main regularities of the changes in the attitude to the marriage and sexual behavior of men and women in the contemporary society on the example of the examination of 1000 persons from the western regions of Ukraine, are presented

Scientific principles for the identification of endocrine-disrupting chemicals: a consensus statement

Endocrine disruption is a specific form of toxicity, where natural and/or anthropogenic chemicals, known as "endocrine disruptors" (EDs), trigger adverse health effects by disrupting the endogenous hormone system. There is need to harmonize guidance on the regulation of EDs, but this has been hampered by what appeared as a lack of consensus among scientists. This publication provides summary information about a consensus reached by a group of world-leading scientists that can serve as the basis for the development of ED criteria in relevant EU legislation. Twenty-three international scientists from different disciplines discussed principles and open questions on ED identification as outlined in a draft consensus paper at an expert meeting hosted by the German Federal Institute for Risk Assessment (BfR) in Berlin, Germany on 11-12 April 2016. Participants reached a consensus regarding scientific principles for the identification of EDs. The paper discusses the consensus reached on background, definition of an ED and related concepts, sources of uncertainty, scientific principles important for ED identification, and research needs. It highlights the difficulty in retrospectively reconstructing ED exposure, insufficient range of validated test systems for EDs, and some issues impacting on the evaluation of the risk from EDs, such as non-monotonic dose-response and thresholds, modes of action, and exposure assessment. This report provides the consensus statement on EDs agreed among all participating scientists. The meeting facilitated a productive debate and reduced a number of differences in views. It is expected that the consensus reached will serve as an important basis for the development of regulatory ED criteria

Determination of aflatoxin M1 and deoxynivalenol biomarkers in infants and children urines from Bangladesh

The mycotoxins aflatoxin B1 (AFB1) and deoxynivalenol (DON) are found worldwide in crops and dietary staples. The prevalence and levels of these contaminants can vary greatly, and data in Bangladeshi food commodities are scarce. To characterize human exposure, we have conducted biomonitoring, analyzing AFM1 (a metabolite of AFB1) and DON levels in urines of adult cohorts in Bangladesh. Yet, AFM1 and DON occurrence has not been studied in the very young population of this country. Thus, the same methods, HPLC-FD for AFM1 and LC–MS/MS for DON analysis, were now applied to determine these biomarkers in urines of infants (n = 49) and young children (n = 105) in Rajshahi and Dhaka district. Overall, AFM1 and DON detection frequency was 43.5% and 33.4%, with 34.7% and 11.5% in infant and 47.6% and 39.4% in children urines, respectively. The mean AFM1 levels in all infants (9.1 ± 14.3, max 55.6 pg/mL) and children (8.8 ± 12.9, max 75.3 pg/mL) were not significantly different. The AFM1 mean level was slightly higher in Dhaka (9.4 ± 12.4) compared to Rajshahi (8.5 ± 13.9 pg/mL) district. The average DON level was about 2-fold higher in infant (3.8 ± 2.9, max 6.8 ng/mL) than children urines (1.6 ± 1.8, max 8.6 ng/mL), and higher in Rajshahi (2.1 ± 2.3 ng/mL) than Dhaka (1.4 ± 1.6 ng/mL) district. The biomarker-based estimated average daily DON intake (29.6 ± 108.3 ng/kg bw in infants and 36.4 ± 81.8 ng/kg bw in children) or the maximum exposure (560 ng/kg bw) do not exceed the current maximum provisional tolerable daily intake value of 1 µg/kg bw for DON, although DON exposure in infants and children is higher than that of Bangladeshi adults. The AFM1 urine levels in young children are somewhat lower than those found previously in adult cohorts in Bangladesh, but the frequent detection of this biomarker for AFB1 exposure raises further concerns, also for this vulnerable part of the population. Therefore, continuous surveillance for aflatoxins in Bangladeshi food commodities is clearly required, first to identify major sources of intake and then to reduce exposure