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The vast majority of toxicity studies and risk assessments deals with single chemicals. In reality, however, humans are exposed simultaneously to a large number of chemicals, indicating that exposure assessment and safety evaluation should focus on mixtures rather than on single chemicals. This review on the toxicology of chemical mixtures covers widely varying issues, ranging from the basic concepts and terminology of joint action and interaction of chemicals to different designs for studying the toxicity of mixtures. Literature data indicate that exposure to mixtures which contain low levels of chemicals, levels lower than their no observed adverse effect levels (NOAELs), can exert toxic effects whether their components have similar modes of action or not. Different approaches and examples of studies on priority real-life mixtures, strategy and guidelines for mixture risk assessment as well as challenges ahead are also presented., Većina toksikoloških studija i evaluacija rizika odnose se na pojedinačne hemikalije. Međutim, u realnom okruženju izloženi smo istovremeno velikom broju hemikalija, što ukazuje da bi pri proceni izloženosti i rizika trebalo posmatrati smeše, a ne samo pojedinačne hemikalije. Ovaj pregledni rad o toksikologiji hemijskih smeša pokriva više stavki, od osnovnih koncepata i terminologije zajedničkog dejstva i interakcija hemikalija do različitih modela za ispitivanje toksičnosti smeša. Literaturni podaci ukazuju na činjenicu da izloženost smešama koje sadrže niske nivoe hemikalija, nivoe koji su niži od njihovih doza bez štetnog efekta (No observed adverse effect level - NOAEL) vrednosti, može rezultirati toksičnim odgovorom bez obzira da li komponente smeše imaju ili ne sličan način dejstva. Dati su i različiti pristupi i primeri koncepata i modela procene toksičnosti prioritetnih smeša iz realnog života, strategija i smernice, kao i dalji izazovi.

Тодор Манојловић, песник, драмски писац, есејиста, књижевни и ликовни критичар и преводилац, оставио је за собом значајну, али недовољно истражену заоставштину. Учествовао је у рађању модерне књижевости у Мађарској својим деловањем у књижевном покрету Ендре Адија, проучавао је ренесансу на изворима, у Италији, а у исто време присуствовао почецима италијанског футуризма и, на основу ових искустава, израстао у естету и ерудиту ренесансног типа. Писањем, књижевном, ликовном и позоришном критиком бавио се преко педесет година. Својом зрелошћу и ширином познавања класичне и модерне књижевности и уметности утицао је на обнову наше, још непосредно пре и за време Првог светског рата. Песмама, драмама и критичким текстовима учествовао је у замаху који је модернистички покрет у свим областима уметничког стваралаштва добио у новоствореној држави – Краљевини Срба, Хрвата и Словенаца, а након ње Југославији. После изгнанства у Зрењанин, које је уследило након Другог светског рата као последица његовог учешћа у културном и јавном животу у окупираном Београду, Тодор Манојловић се није сасвим повукао из јавности. Његова настојања да му се објављују текстови и књиге у великој мери су остала без одговора, нарочито у првој деценији након Другог светског рата. Његово стваралаштво било је предмет истраживања и тумачења мањег броја ентузијаста, поштовалаца његовог дела и пријатеља, али и опонената, а после његове смрти рукописна грађа и остала заоставштина једним делом је поклоњена, продата или изгубљена. Први покушај институционализованог бављења наслеђем Тодора Манојловића учињен је седамдесетих година 20. века у Историјском архиву у Зрењанину, у који је доспео део рукописне заоставштине. Оснивањем часописа Улазница, 1967. године, учињена је почаст знаменитом грађанину Зрењанина објављивањем његових песама и библиографије. Деведесетих година обновљено је интересовање за дела Тодора Манојловића, у чему је Градска народна библиотека „Жарко Зрењанин“ у Зрењанину, оснивач Фонда „Тодор Мано, Todor Manojlovic, poet, playwright, essayist, literary and art critic and translator, left behind an important but under-explored legacy. He participated in the birth of modern literature in Hungary through the actions of the literary movement of Adi Endre. Manojlović also studied the Renaissance in Italy and, at the same time, attended the begginig of Italian Futurism and, based on these experiences, grew in erudite and esthete of wide knowledge. Over fifty years he dealt with writing, literary, artistic and theatrical criticism. His maturity and breadth of knowledge of classical and modern literature and art influenced the renewal of our art before and during World War II. With his poems, dramas and critical writings Manojlović participated in the modernist movement in all areas of artistic creativity in the new state - the Kingdom of Serbs, Croats and Slovenes, later Yugoslavia. After exile in Zrenjanin, which followed the Second World War as a result of his participation im, cultural and public life in occupied Belgrade, Todor Manojlovic is not completely withdrawn from the public. His efforts to publisharticles and books were largely unanswered, especially in the first decade after the Second World War. His art has been the subject of research and interpretation of a small number of enthusiasts, admirers of his work and friends and opponents, and after his death, manuscripts, and other legacy were partly donated, sold or lost. The first institutional attempts to deal with the legacy of Todor Manojlovic were made in the seventies, in Historical Archive in Zrenjanin, which has got his manuscript legacy. Journal Ulaznica, found in 1967, made an homage to the famous citizen of Zrenjanin publishing his poems and bibliographie. In nineties, interest of works of Todor Manojlovic was renewed, and Public Library "Zarko Zrenjanin", founder of "Todor Manojlovic" Foundation had the largest share...

Kada određena supstacija uđe u organizam, njeno toksično delovanje se klinički može manifestovati na razne načine, zavisno od vrste poremećaja prouzrokovanog na nivou ćelije. Vezivanjem za određene endogene molekule, toksična jedinjenja mogu prouzrokovati poremećaj genske ekspresije (neoplazija, teratogeneza), poremećaj tekućih ili trenutnih aktivnosti ćelije (tremor, konvulzije, spazam, aritmija), poremećaj integriteta ćelije (poremećaj sinteze proteina, poremećaj funkcije ćelijske membrane, smrt ćelije) i poremećaj odnosa sa drugim ćelijama (poremećaj u hemostazi – krvarenje). Najteži poremećaji, koji nastaju usled vezivanja hemijskih supstancija sa takozvanim „kritičnim proteinima” (DNK, RNK), klinički se mogu manifestovati kao: mutageneza, karcinogeneza, teratogeneza i imunotoksičnost., When chemical compound enter the body, its toxic effect may clinical to demonstrate in different way, depend from kind of disturbance, what that substance induced in the cell. Binding for endogenous molecules toxic substances can induced disturbance of gens expression (neoplasia, teratogenesis), disturbance of curently activities of cell (tremor, convulsions, spasm, aritmia), disturbance of integrity of cell (disturbance of sinthesis of proteins, disturbance of function of cell membrane, death of cell) and disturbance of relation with other cells (disorders of hemostasis – bleeding). The most serious disturbances which may to begin because of binding chemical substances for so-called “critical proteins” (DNA, RNA) clinical may to demonstrate as: mutagenesis, carcinogenesis, teratogenesis and as immunotoxicity.

Wild population of Hypericum perforatum growing in Western Serbia was analyzed for the content of important environmental pollutants cadmium, mercury and lead. Metal contents were determined by inductively coupled plasma optical emission spectrometry. Obtained results showed that levels of mercury and lead were under while cadmium concentrations exceeded limits recommended for medicinal plants. High levels of cadmium in investigated plants can be the result of soil enriched with cadmium as well as the ability of Hypericum perforatum to accumulate cadmium.

In this study we present the results of arsenic concentration in water samples from public water supply system of city Zrenjanin and three Northern municipalities Elemis, Taras and Melenci taken every month during 2002, 2007 and 2011. Total arsenic content was determined using AAS technique with hydride generation system. Determined levels of arsenic in all investigated samples were more than 10 times higher than the maximum permissible limit recommended by WHO (10 mu g/L) and even reached levels higher than 300 mu g/L. During 2011 drinking water from 44 pump wells in Zrenjanin was also analyzed showing that more than 50% of pump wells contain more than 10 mu g As/L. These findings can be explained by geological characteristics of Northern region of Serbia belonging to Pannonian Basin which has aquifers that contain high concentration of naturally occurring arsenic. Results suggest that arsenic levels in this Serbian region are even higher than in other countries in the Pannonian Basin. Having in mind profound deleterious effects of arsenic on human health, different social, economical and technological measures are required in order to reduce arsenic concentration to acceptable limits.

Cadmium (Cd) is today one of the most significant metal poisons, both in the area of professional as well as of eco toxicology. In the organism, cadmium has a harmful effect on the kidneys, liver, bones, testicles, etc., and, based on evidence in humans that it causes lung carcinoma, it has been placed in the first group of carcinogens. In spite of numerous data in literature on the harmful effects of cadmium, the interactions between cadmium and bioelements as a significant mechanism for cadmium toxicity have still not been sufficiently explained. Since the data so far point to a positive effect of supplementation with certain bioelements regarding toxicity and cadmium content in the organism, the objective of this work was to investigate the effect of increased simultaneous intake of magnesium, zinc and copper on urinary elimination of cadmium in rabbits exposed to cadmium. Rabbits were divided into two groups: Cd group - for a period of 28 days the animals received per os 10 mg Cd/kg b.m/day and Cd+(Mg+Zn+Cu) group - 10 mg Cd/kg b.m. + 40 mg Mg/kg b.m, 20 mg Zn/kg b.m. and 10 mg Cu/kg b.m/day. Daily urine was collected on days 0, 10, 15, 17, 19, 21, 23, 25, and 28 of the experiment. Following decomposition of urine samples with the help of concentrated HNO3 and HClO4 (4:1), the metal concentration was determined using the method of atomic absorption spectrophotometry. Supplementation with magnesium, zinc and copper did not result in significant changes in the elimination of cadmium through urine in animals poisoned with cadmium, in comparison with the animals that were administered only cadmium, while the concentration of all three applied bioelements in urine was significantly increased. It can be concluded that the simultaneous administration of increased doses of zinc, copper and magnesium does not have a positive effect on the elimination of cadmium in conditions when rabbits are poisoned with cadmium., Kadmijum (Cd) je danas jedan od najznačajnijih metalnih otrova, kako u oblasti profesionalne tako i ekotoksikologije. U organizmu, Cd štetno deluje na bubrege, jetru, kosti, testise itd., a na osnovu dokaza da na ljudima izaziva karcinom pluća svrstan je i u I grupu karcinogena. I pored brojnih literaturnih podataka o štetnim efektima Cd, interakcije kadmijuma i bioelemenata kao značajnog mehanizma toksičnosti kadmijuma, još uvek nisu dovoljno razjašnjene. S obzirom na to da dosadašnji podaci ukazuju na pozitivan efekat suplementacije pojedinim bioelementima na toksičnost i sadržaj kadmijuma u organizmu, cilj ovog rada je bio da se ispita uticaj povećanog istovremenog unosa magnezijuma, cinka i bakra na urinarnu eliminaciju kadmijuma kod kunića izloženih kadmijumu. Kunići su bili podeljeni u dve grupe: I Cd grupa - životinje su 28 dana primale per os 10 mg Cd/kg t.m/dan i II grupa - Cd+ (Mg+Zn+Cu): 10 mg Cd/kg t.m. + 40 mg Mg/kg t.m, 20 mg Zn/kg t.m. i 10 mg Cu/kg t.m/dan. Dnevni urin je sakupljan 0, 10, 15, 17, 19, 21, 23, 25. i 28. dana eksperimenta. Nakon razaranja uzoraka urina uz pomoć koncentrovanih HNO3 i HClO4 (4:1), koncentracija metala je određena metodom atomske apsorpcione spektrofotometrije. Suplementacija magnezijumom, cinkom i bakrom nije dovela do značajne promene u eliminaciji kadmijuma urinom kod životinja trovanih kadmijumom u poređenju sa životinjama koje su primale samo kadmijum, dok je koncentracija sva tri primenjena bioelementa u urinu bila značajno povećana. Može se zaključiti da istovremeno davanje povećanih doza cinka, bakra i magnezijuma ne ispoljava pozitivan efekat na eliminaciju kadmijuma u uslovima trovanja kunića kadmijumom.

The present study is designed to investigate whether magnesium (Mg) supplementation may prevent Cd-induced alterations in zinc (Zn), copper (Cu), and magnesium (Mg) status in rabbits. For this purpose, the concentrations of Zn, Cu, and Mg were estimated in blood, urine, and organs (brain, heart, lungs, liver, kidney, spleen, pancreas, skeletal muscle, and bone) of rabbits given Cd (10 mg/kg b.w.) and rabbits cotreated with Mg (40 mg/kg b.w.) orally, as aqueous solutions of Cd chloride and Mg acetate every day for 4 weeks. Samples were mineralized with conc. HNO3 and HClO4 (4:1) and metals concentrations were determined by atomic absorption spectrophotometry (AAS). Magnesium supplementation succeeded to overcome Cd-induced disbalance of investigated bioelements. Beneficial effects of Mg were observed on Zn levels in blood and urine, on Cu levels in urine, and on Mg levels in blood. Magnesium pretreatment also managed to counteract or reduce all Cd-induced changes in levels of Cu and Mg in organs, while it did not exert this effect on Zn levels. These findings suggest that enhanced dietary Mg intake during Cd exposure can have at least partly beneficial effect on Cd-induced alterations in homeostasis of zinc, copper, and magnesium.

Cadmium (Cd) has been recognised as one of the most important environmental and industrial pollutants, and up-to-date investigations have shown that one of the mechanisms of its toxicity is associated with the induction of oxidative stress. The aim of this study was to determine the connection between acute oral and intraperitoneal exposure to Cd and parameters indicative of oxidative stress in the plasma of rats, as well as to examine the potential protective effect of magnesium (Mg) in conditions of acute oral and intraperitoneal Cd poisoning. The experiment was performed on male albino Wistar rats (n=40) randomly divided into control group, Cd-or group that received 30 mg kg(-1) b.w. Cd by oral gavage, Cd+Mg-or group that orally received 50 mg kg(-1) b.w. Mg one hour before oral Cd, Cd-ip group that received 1.5 mg kg(-1) b.w. Cd intraperitoneally, and Cd+Mg-ip group that intraperitoneally received 3 mg kg(-1) b.w. Mg 10 min before intraperitoneal Cd. The animals were sacrificed 24 h after treatment and the following parameters were measured: superoxide-dismutase activity, superoxide anion, total oxidative status, advanced oxidation protein products, and malondialdehyde. All parameters of oxidative stress in rat plasma were negatively affected by Cd treatment with more pronounced negative effects after intraperitoneal treatment, with the exception of superoxide dismutase (SOD) activity. Although both oral and intraperitoneal Mg pretreatment had protective effects, more pronounced beneficial effects were observed after oral administration, since it managed to completely prevent Cd-induced changes in the investigated parameters. The observed results support the use of Mg as potential protective agent against toxic effects caused by Cd.

Background/Aim. The beneficial effects of medicinal plants are well-known from the ancient times. However, expansion of phytopharmacy and phytotherapy occured during the last decades. Medicinal plants can absorb environmental contaminants from the ground and consequently may cause harmful effects on human health. Quality control usually comprises standard methodology which includes macroscopic identification and examination of active ingredients. Additionaly, there is a permanent need to control the level of pollutants in herbs, with a particular attention to the level of toxic metals. In this study we estimated the level of contamination by determining the content of cadmium (Cd) in the herbs of Hypericum perforatum and Thymus serpyllum collected from the different localities of the mountains Rtanj and Ozren. Methods. Herbs of investigated plants were collected during July 2005 from various localities of Rtanj and Ozren mountains. After drying, homogenization and mineralization, Cd content was determined by atomic absorption spectrophotometry. Results. The obtained results show that Cd content varies significantly in Hypericum perforatum samples collected. The lowest Cd level was found in samples from the one of Rtanj localities (0.25 mg Cd/kg), while the highest was observed in Hypericum perforatum from Ozren locality (1.24 mg/kg). Levels of Cd in the three of four investigated localities were higher than pro posed by WHO (0.3 mg/kg dried herb material). In all investigated samples of Thymus serpyllum herbs Cd levels were below the limit of detection of analytical method (0.2 mg Cd/kg dried materials). Conclusion. This work contributes to the issue of Cd content in Hypericum perforatum and Thymus serpyllum grown in localities of Rtanj and Ozren, and implies the importance for systemic control of Cd content in Hypericum species in order to provide safety of their preparations. Furthermore, regarding Cd toxicity, maximal permissible level of Cd in plant material sho, Uvod/Cilj. Lekovitost nekih biljnih vrsta bila je poznata čoveku još pre naše ere. Međutim, do ekspanzije fitofarmacije i fitoterapije dolazi tek poslednjih decenija. Lekovite biljke usled zagađenja životne sredine mogu da apsorbuju prisutne zagađivače. Kvalitet biljnih sirovina prati se standardnim metodama koje se prvenstveno odnose na identifikaciju biljne vrste i ispitivanja aktivnih principa. Ipak, i pored toga, uočena je potreba za kontrolisanjem i praćenjem nivoa zagađivača, među kojima značajno mesto zauzimaju toksični metali. U ovom radu ispitivan je sadržaj kadmijuma (Cd) u herbi dve biljne vrste, Hypericum perforatum L. i Thymus serpyllum L. koje su prikupljene sa različitih lokaliteta planina Rtanj i Ozren, sa ciljem procene nivoa kontaminacije. Metode. Herbe ispitivanih lekovitih biljaka sakupljene su tokom jula 2005. godine sa različitih lokaliteta planina Rtnja i Ozrena. Nakon sušenja, homogenizacije i mineralizacije, sadržaj Cd određivan je metodom atomske apsorpcione spektrofotometrije. Rezultati. Dobijeni rezultati ukazali su na značajne varijacije sadržaja Cd u sakupljenim uzorcima Hypericum perforatum. Najniži sadržaj Cd od 0,25 mg Cd/kg dobijen je u uzorku sa lokaliteta Rtnja, dok je najviši nivo Cd određen u uzorku Hypericum perforatum sa lokaliteta Ozrena (1,24 mg/kg). Dobijene vrednosti sadržaja Cd u herbi Hypericum perforatum sa tri od četiri ispitivana lokaliteta bile su iznad vrednosti koju preporučuje SZO (0,3 mg/kg osušene droge). U svim ispitivanim uzorcima Thymus serpyllum nivoi Cd bili su ispod nivoa detekcije primenjene analitičke tehnike (0,2 mg Cd/kg osušene herbe). Zaključak. Rezultati ovog rada doprineli su istraživanju sadržaja Cd u biljnim vrstama Hypericum perforatum i Thymus serpyllum koje rastu na lokalitetima Rtnja i Ozrena i ukazuju na potrebu uvođenja sistematske kontrole sadržaja Cd u Hypericum vrstama radi bezbedne upotrebe preparata izrađenih na bazi ovih biljnih vrsta. Imajući u vidu toksičnost Cd nameće se potreba da