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Humans are exposed to the chemicals from very different sources. Therefore, the exposure assessment should be focused on mixtures rather than single chemicals. In this study, bioelements (Zn and Cu) homeostasis effects of mixture of Cd and BDE-209, widely spread persistent environmental pollutants, has been evaluated. In order to evaluate the potential of mixture on Zn and Cu homeosthasis in rats kidneys, Wistar rats were treated by oral gavage during 28 days with three doses of Cd 2.5, 7.5, and 15 mg/bw/day, three combinations of Cd with 1000 mg BDE-209/kg/day, and water as a control group. Kidney tissue samples were collected, mineralised, and Cu and Zn levels were measured by flame atomic absorbtion spectrophotometer. Possible interactions were evaluated comparing the dose-response curves slopes and lower confidence limit of Benchmark dose of 10% (BMDL10) were calculated by PROAST software (RIVM, Netherlands). Cd alone can disturb Zn in kidneys and calculated BMDL10 was 1.713 mg Cd/kg/day, while in combination with BDE-209 it was 1.719 mg/kg/day. Cd disturbs Cu in kidney in significantly higher dose of 5.679 mg Cd/kg/day. However, in combination with the BDE-209, derived BMDL10 was 10 times lower, 0.517 mg Cd/kg/day. Dose-response curve slope for the effect on Cu was significantly lower in the case of mixture effect than in the case of Cd effect. Since Cu plays a major role in the blood cells creation and health of other systems, our results indicate more potent activity of the mixture than single Cd. Ljudi mogu biti izloženi hemikalijama iz različitih izvora, te je potrebno procenjivati efekte na bazi izloženosti smešama hemikalija, pre nego pojedinačnim hemikalijama. U studiji je analiziran uticaj smeše Cd i BDE-209, široko rasprostranjenih zagađujućih perzistentnih supstanci, na homeostazu bioelemenata, cinka (Zn) i bakra (Cu). U cilju evaluacije potencijala smeše da naruši homeostazu Zn i Cu u bubrezima pacova, Wistar pacovi su oralnom gavažom bili tretirani tokom 28 dana dozama Cd od 2,5, 7,5 i 15 mg/kg/dan, kombinacijama ove tri doze sa 1000 mg BDE-209/kg/dan i vodom kao kontrolom. Tkivo bubrega je izdvojeno, zatim mineralizovano, a sadržaj Zn i Cu je meren atomskom apsorpcionom spektrofotometrijom. Moguće interakcije su procenjivane poređenjem nagiba krivih doza-odgovor, a izračunate su i donje granice pouzdanosti Benchmark doze od 10% (BMDL10) korišćenjem PROAST softvera (RIVM, Holandija). Cd primenjen sam utiče na homeostazu Zn u bubregu i izračunata BMDL10 iznosi 1,713 mg/kg/dan, dok u kombinacji sa BDE-209 iznosi 1,719 mg/kg/dan. Cd ometa homeostazu Cu u bubregu pacova i BMDL10 iznosi 5,679 mg/kg/dan, dok je u kombinaciji sa BDE-209 BMDL 10 puta niža i iznosi 0,517 mg/kg/dan. Nagib krive doza odgovor za smešu Cd i BDE-209 bio je daleko niži od nagiba krive doza-odgovor za Cd. S obzirom na to da Cu igra značajnu ulogu u nastanku krvnih ćelija, ali i u očuvanju durgih sistema organa, dobijeni rezultati iziskuju pažnju zbog daleko potentnijeg uticaja smeše na nivo Cu u odnosu na uticaj samog Cd. VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beograd

The microelements chromium, cobalt and nickel are necessary for the proper functioning of the organism. At higher concentrations, they can cause toxic effects (organ disfunction, genetic damage). They are widespread in the enviroment. They reach our body through food, water, air and/or skin. The aim of this study was to determine the reference values of chromium, cobalt and nickel in the blood of adult residents of Belgrade and determine the degree of influence of individual, socioeconomic factors and lifestyle habits on blood levels of these metals. The study population consisted of adults, healthy population, 18 to 65 years of age, who were voluntary blood donors. The study included 715 men (72.7%) and 269 women (27.3%). Blood collected in vacutainers with heparin, was used for analysis. 984 samples were analysed. The metals were determined using inductively coupled plasma mass spectrometry (7700x, Agilent, USA), with octopol reactive system and micro-flow nebulizer. The average age of participants was 37.2 10.8. The reference values of the analysed metals, shown as the 95 percentile, were 0.95µg/L, 0.62µg/L and 1.46µg/L for chromium, cobalt and nickel, respectively, and were in good correlation with the values obtained in biomonitoring studies conducted in Europe. This study showed that population of Serbian origin had significantly lower blood concentrations of chromium, that cobalt blood levels in women were significantly higher and cobalt and nickel levels increased with age in both sexes. Education and economic status, cigarette smoking and sports did not significantly affect the levels of these metals in the blood. Mikroelementi hrom, kobalt i nikl su potrebni za pravilno funkcionisanje organizma. U većim koncentracijama mogu ispoljiti toksične efekte poput ometanja pravilne funkcije organa i dovesti do genetskih oštećenja i karcinogeneze. Široko su rasprostranjeni u životnoj sredini. Putem hrane, vode, vazduha i/ili kože dospevaju u naš organizam. Cilj rada bio je da se utvrde referentne vrednosti hroma, kobalta i nikla u krvi odraslih stanovnika grada Beograda, kao i stepen uticaja individualnih, socioekonomskih faktora i životnih navika na nivoe ovih metala u krvi. Ispitivanu populaciju je činilo odraslo, zdravo stanovništvo,ukupno 715 muškaraca (72,7%) i 269 žena (27,3%) od 18 do 65 godina starosti, koji su bili dobrovoljni davaoci krvi. Za analizu je korišćena krv sakupljana u vakutejnere sa heparinom. Analizirano je 984 uzoraka. Koncentracija metala je određena metodom masene spektrometrije sa induktivno spregnutom plazmom (7700x, Agilent, USA), sa oktopol reaktivnim sistemom i „micro‐flow“ raspršivačem. Prosečna starost ispitanika iznosila je 37,210,8 godina. Referentne vrednosti ispitivanih metala u krvi, prikazane kao 95. percentil su 0,95 µg/L, 0,62 µg/L i 1,46 µg/L za hrom, kobalt i nikl, redom, su u dobroj korelaciji sa vrednostima dobijenim u biomonitoring studijama sprovedenim u Evropi. Istraživanje uticaja individualnih faktora je pokazalo da je hrom izmeren u značajno nižim koncentracijama kod stanovništva srpske nacionalnosti, da su nivoi kobalta u krvi žena značajno viši i da se nivoi kobalta i nikla povećavaju sa starenjem kod oba pola. Obrazovanje i ekonomski status, pušenje cigareta i bavljenje sportom ne utiču statistički značajno na nivoe ovih metala u krvi. VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beograd

The rapid global growth of drugs production and consumption undoubtedly leads to contamination of the environment with pharmaceutical substances, as well as the products of their decomposition and metabolism. Therefore, the ecosystem is exposed to pharmaceutical waste, what may result in various unwanted effects, such as the development of microorganism’s resistance to antibiotics. A brief review of the European Union regulations, as well as the United States of America and Australia amadments, revealed the diversity of approaches and regulatory measures adopted with the purpose of proper hazardous waste handling. However, none of proposed systems show enviable results. We conducted the research in the period of March-May 2020, to find out how citizens of Bor municipality handle the pharmaceutical waste. A total of 226 responses were collected by surveying patients, in person and in electronic form. The obtained results were analyzed using the statistical software SPSS 21.0. The presented results show that the awareness of the potential toxicity of pharmaceutical waste is developed in more than a third of respondents (37.5%), but also low level of knowleadge about the proper way of disposing generated waste. Over 36% of men and 42% of women throw away their medicines together with other household waste, while 9% of men and 11% of women take them to pharmacies. The legal regulations and accompanying guidelines, together with appropriate media campaign, would contribute to a better understanding of the given problem and the adoption of new citizens habits when it comes to hazardous waste handling. Brz rast proizvodnje i potrošnje lekova na globalnom nivou, nesumnjivo dovodi do kontaminacije životne sredine farmaceutskim supstancama, njihovim metabolitima, kao i proizvodima njihove dodatne razgradnje u životnoj sredini. Posledično, živi svet biva izložen uticaju farmaceutskog otpada usled čega dolazi do ispoljavanja različitih neželjenih efekata, kao, na primer, razvoja rezistencije mikroorganizama na antibiotike. Kratkim pregledom regulative zemalja članica Evropske unije, Sjedinjenih Američkih Država i Australije, uočena je različitost pristupa i regulatornih mera donetih u cilju pravilnog rukovanja otpadom, između ostalih i farmaceutskim otpadom, pri čemu ni jedan sistem ne pokazuje zavidne rezultate. Istraživanjem rađenim u periodu mart-maj 2020. godine pokušali smo da dođemo do saznanja koliko je razvijena svest građana opštine Bor, o postojanju farmaceutskog otpada kao posebne kategorije koja može da ugrozi zdravlje ljudi ali i životnu sredinu. Anketiranjem pacijenata, kako ličnim kontaktom, tako i u elektronskoj formi prikupljeno je ukupno 226 odgovora, a dobijeni rezultati analizirani su pomoću statističkog softvera SPSS 21.0. Dobijeni rezultati pokazuju da je svest o štetnosti farmaceutskog otpada razvijena kod više od trećine ispitanika (37,5%), ali i postojanje niskog stepena informisanosti o pravilnom načinu zbrinjavanja generisanog otpada. Zbog toga, preko 36% muškaraca i 42% žena lekove baca u komunalni otpad., dok ih 9% muškaraca i 11% žena odnosi u apoteke. Dopuna zakonske regulative kao i pratećih pravilnika, propraćena odgovarajućom medijskom kampanjom doprinela bi boljem razumevanju datog problema i usvajanju novih navika kod građana u načinu rukovanja neiskorišćenim lekovima iz domaćinstva. VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beograd

Acute poisonings by drugs used for cardiovascular diseases treatment are less frequent than poisonings by other drugs, but often lead to serious disorders in various organ systems and are characterized by relatively high mortality. When it comes to polydrug poisoning by drugs with a depressant effect on the cardiovascular system, hospital care of the patients is necessary. This research aimed to present data on acute poisonings by drugs used in the cardiovascular diseases treatment in the Republic of Serbia in the period 2010- 2018 based on the published Annual reports of the National Poison Control Center of the Military Medical Academy (1). Number of patients examined on suspicion of poisoning by drugs for cardiovascular diseases treatment, in the period 2010-2018, ranged from 4-6% of all examined due to acute drug poisoning per year, while number of hospitalizations due to drug poisoning ranged from 7 to 11% of all hospitalized patients. Of the total number of deaths resulting from drug poisoning, 27% are patients who died due to the poisoning by drugs used for cardiovascular diseases treatment. The most common causes of poisoning in the examined patients were beta blockers (45%), followed by Ca 2+ channel blockers (25%) and ACE inhibitors (21%), and these three groups of drugs are the most common causes in hospitalized patients as well. Lethal outcomes are most often the result of acute poisoning by Ca 2+ channel blockers (50%) and beta blockers (40%), mainly in combination with drugs used in psychiatric illnesses treatment, such as benzodiazepines, antiepileptics and antipsychotics. Akutna trovanja lekovima za lečenje kardiovaskularnih bolesti su ređa u odnosu na trovanja drugim lekovima, ali često dovode do ozbiljnih poremećaja u funkcionisanju različitih sistema organa i karakterišu se relativno visokim mortalitetom. Kada su u pitanju polimedikamentozna trovanja lekovima koji imaju depresorno dejstvo na kardiovaskularni sistem, neophodno je bolničko zbrinjavanje pacijenata. Cilj ovog rada je bio prikazati analizu podataka o akutnim trovanjima lekovima koji se koriste u terapiji kardiovaskularnih oboljenja u Republici Srbiji u periodu od 2010 do 2018. godine na osnovu publikovanih Godišnjaka Nacionalanog centra za kontrolu trovanja Vojnomedicinske akademije (1). Broj pacijenata koji su pregledani pod sumnjom na trovanje lekovima za lečenje kardiovaskularnih bolesti u periodu 2010-2018. godine kretao se od 4-6% svih pacijenata pregledanih usled akutnog trovanja lekovima godišnje, dok se broj pacijenata hospitalizovanih usled trovanja lekovima kretao 7-11% svih hospitalizovanih pacijenata. Od ukupnog broja letalnih ishoda koji su posledica trovanja lekovima, 27% čine pacijenti preminuli zbog trovanja lekovima za lečenje kardiovaskularnih bolesti. Najčešći uzročnici trovanja kod pregledanih pacijenata su beta blokatori (45%), zatim blokatori Ca 2+ kanala (25%) i ACE inhibitori (21%), a ove tri grupe lekova su najzastupljenije i kod hospitalizovanih pacijenata. Letalni ishodi su najčešće posledica akutnog trovanja blokatorima Ca 2+ kanala (50%) i beta blokatorima (40%), uglavnom u kombinaciji sa lekovima koji se koriste u terapiji psihijatrijskih oboljenja poput benzodiazepina, antiepileptika i antipsihotika. VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beograd

Phthalates are commonly used plasticizers for plastic materials. Number of toys are made from plastic materials or are coated with plastic layer. No existence of chemical bound between phthalates and polymer layers means their easy migration. Children’s exposure to phthalates is recognised as a threat to their health, since phthalates interfere with hormones level (endocrine disrupter chemicals – EDC), but can also induce hepatotoxicity, renal toxicity, allergic diseases and astma and disrupt thyroid function. Rulebook on Toy safety (“Official Gazette of RS” No. 78/2019) was published in 2019, to set rules on toys safety and their free movement on the market. Phthalates are prohibited, individually or in combination in a concentration equal to or greater than 0.1% (m/m). Butylbenzyl phthalate (BBP), Di-n- butyl phthalate (DBP), Bis(2-ethylhexyl) phthalate (DEHP) and Diisobutyl phthalate (DIBP) are listed as prohibited, but DIBP restrictions start from July 2023 (1). In accordance with this legislative, laboratory of Institute of Public Health of Serbia “Dr Milan Jovanovic Batut” analyses part of these toys present on the market in Serbia. Total of 232 toy samples were analysed in the last 5 years (2017-2021), by HPLC-DAD. Phthalates are found in 40 samples (17.2%), 10 samples (4.3%) were bellow and 30 (12.9%) exceeded concentration of 0.1% (m/m). The most common elevated phthalates were DEHP and DBP. During 2019 and 2021 no phthalates are found in samples. Constant appearance of new toy manufacturers and control of existing ones demand monitoring of toys present on RS market, for the purpose of children's safety. Ftalati spadaju u najčešće korišćene plastifikatore za plastične materijale. Veliki broj igračaka izrađen je od plastike ili je plastificiran. Usled nepostojanja hemijske veze između ftalata i slojeva polimera, lako može doći do migracije ftalata. Izloženost dece ftalatima prepoznata je kao pretnja po zdravlje, budući da su ftalati klasifikovani u grupu jedinjenja endokrinih ometača (EDC), pošto utiču na promene nivoa hormona, ali takođe mogu dovesti i do oštećenja jetre, bubrega, poremećaja rada štitaste žlezde, alergijskih bolesti i astme. Pravilnik o bezbednosti igračaka Republike Srbije („Službeni glasnik RS” broj 78/2019) donešen je u cilju uspostavljanja pravila o bezbednosti igračaka i njihovom slobodnom kretanju na tržištu. Upotreba ftalata kao plastifikatora zabranjena je, pojedinačno ili u smeši, ako je koncentracija jednaka ili veća od 0,1% (m/m). Na listi zabranjenih ftalata su: butilbenzil ftalat (BBP), di-n-butil ftalat (DBP), di-2-etilheksil ftalat (DEHP), kao i di-izo-butil ftalat (DIBP) čija zabrana stupa na snagu od jula 2023. godine (1). U skladu sa postojećim propisima, laboratorija Instituta za javno zdravlje Srbije „Dr Milan Jovanović Batut“ analizira deo igračaka prisutnih na tržištu u Srbiji. Tokom prethodnih 5 godina (2017-2021) analizirano je ukupno 232 uzoraka igračaka. Ftalati su nađeni u 40 uzoraka (17,2%), od kojih je 10 uzoraka (4,3%) imalo ispod, a 30 (12,9%) preko granične koncentracije od 0,1% (m/m). Najčešće povišeni ftalati su DEHP i DBP. Tokom 2019. i 2021. godine u uzorcima nije utvrđeno prisustvo ftalata. Usled stalne pojave novih proizvođača igračaka, kao i kontrole već prisutnih, neophodan je redovan monitoring igračaka na tržištu RS radi bezbednosti dece. VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beograd

According to the current regulations in Serbia, the cultivation and sale of hemp-based products (Cannabis sativa L.) containing up to 0.3% of substances from the group of tetrahydrocannabinol is allowed. ∆-9-tetrahydrocannabinol (THC) is responsible for the psychoactive effects and the development of cannabis addiction. A growing number of products based on parts or the whole cannabis plant are on free sale. Since cannabis is the most commonly used psychoactive substance, there is a greater need for quick and easy detection in the body. The Aim of this project was to examine the effect of commercial cannabis-based products consuption on urine THC detection by using immunochromatographic test strips. Eight healthy volunteers consumed commercially available hemp-based products (four tea products, two ground and two whole seeds products). The products were consumed according to the instructions given by the manufacturer, for three consecutive days, and on the fourth day the first morning urine was tested for the presence of THC using multicomponent One Step Rapid Test®-Ameritek® test strips. Urine samples from five subjects gave a negative test result, and three samples, from subjects who consumed hemp ground seeds and tea in bulk, gave a positive THC test. Further analysis of positive urine samples by the conformative method (HPLC-PDA) did not prove the presence of THC. Consumption of certain commercial cannabis-based products can lead to false-positive results in the detection of THC in urine by immunochromatographic test strips. Therefore, it is necessary to perform further analysis of urine by conformative methods. Prema važećoj regulativi u Srbiji je dozvoljeno gajenje i prodaja proizvoda na bazi konoplje (Cannabis sativa L.) koji sadrže do 0,3% supstanci iz grupe tetrahidrokanabinola od kojih se ∆-9-tetrahidrokanabinolu (THC) pripisuju psihoaktivni efekti i razvoj zavisnosti povezan sa zloupotrebom kanabisa. U slobodnoj prodaji se nalazi sve veći broj proizvoda baziranih na delovima ili celoj biljci kanabisa. S obzirom na to da je kanabis najčešće korišćena psihoaktivna supstanca postoji i veća potreba za brzom i lakom detekcijom u organizmu. Cilj ovog rada je ispitati uticaj konzumiranja komercijalnih proizvoda na bazi konoplje na dokazivanje THC u urinu imunohromatografskim test trakama (1,2). U ispitivanje je uključeno osam zdravih dobrovoljaca koji su konzumirali komercijalno dostupne preparate na bazi konoplje (četiri čaja, dva mlevena i dva cela semena). Preparati su konzumirani prema uputstvu datom od strane proizvođača, tri uzastopna dana, a četvrtog dana je vršeno testiranje prvog jutarnjeg urina na prisustvo THC, upotrebom višekomponentnih One Step Rapid Test®‐Ameritek® test traka. Uzorci pet ispitanika su dali negativan rezultat testa, a tri uzorka, poreklom od ispitanika koji su konzumirali mleveno seme konoplje i čaj u rinfuzu, dala su pozitivan test na THC. Daljom analizom urina koji su dali pozitivan rezultat, konfirmativnom metodom (HPLC-PDA) nije dokazano prisustvo THC. Konzumacija pojedinih preparata na bazi konoplje, koji se mogu naći u slobodnoj prodaji, može da dovede do pojave lažno pozitivnih rezultata pri dokazivanju THC u urinu imunohromatografskim test trakama, zbog čega je neophodno izvršiti dalju analizu urina konfirmativnim metodama. VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beograd

One of the most polluted cities in Serbia and Europe is Bor, due to mining and smelting processes in Mining-Metallurgical Complex in Bor. Mining activities release mainly SO2 and paritculate matter in air (1) and, as arsenic is usually found in copper and lead ores, air quality monitoring in Bor has been showing its presence in exceeded annual limit concentrations in past few years. Exposure to arsenic is related with anemia, skin changes, peripheral neuropathy and cancer development. This study was carried out to assess children’s and adult’s exposure to arsenic bound to PM10 and to charcterize risk from their exposure through the air in the city of Bor. Mean yearly concentrations of arsenic were used from Reports of the Serbian Enviromental Protection Agency, for measuring stations: Bor- City park, Bor 1, Bor 2 and Bor-Jugopetrol. The USEPA method was used to assess non- carcinogenic and carcinogenic risk, which classifies non-carcinogenic risk as acceptable (1) based on hazard quotient (HQ) values for three main exposure pathways, while cancer risk classification is based on CR values also as acceptable (1×10 -4 ) (2). HQinh values exceeded safe level both for children and adults on all measuring stations, describing risk as unacceptable via inhalation exposure. Unacceptable carcinogenic risk for children was calculated on measuring station Bor- Jugopetrol and for adults on measuring stations Bor-City park, Bor 1 and Bor-Jugopetrol. Actions for reduction of arsenic release into the air should be taken due to obtained results for city of Bor. Grad Bor spada među najzagađenije gradove u Republici Srbiji i Evropi. Najveći izvor zagađenja u ovom gradu predstavlja rudnik bakra, Rudarsko-topioničarski basen Bor, usled emisije, predominantno, SO2 i suspendovanih čestica (1). Arsen je čest pratilac ruda bakra i olova, te se iz godine u godinu monitoringom kvaliteta vazduha uočava njegovo prisustvo u koncentracijama koje prelaze dozvoljene godišnje granice. Izloženost arsenu može dovesti do razvoja anemije, promena na koži, periferne neuropatije, ali i razvoja karcinoma. Cilj rada bio je da se proceni izloženost i okarakteriše rizik dece i odraslih od izloženosti arsenu iz PM10 čestica tj. putem zagađenog vazduha u gradu Boru. Vrednosti prosečnih godišnjih koncentracija arsena u vazduhu su preuzete iz godišnjih izveštaja Agencije za zaštitu životne sredine, za merne stanice: Bor-Gradski park, Bor 1, Bor 2 i Bor-Jugopetrol. Zdravstveni rizik je procenjen metodologijom koju preporučuje Američka agencija za zaštitu životne sredine. Na osnovu vrednosti količnika hazarda (HQ) za oralni, inhalacioni i dermalni put unosa, ne- karcinogeni rizik se klasifikuje kao prihvatljiv (1), dok se karcinogeni rizik klasifikuje na osnovu vrednosti CR, takođe kao prihvatljiv (1×10 -4 ) (2). Izračunate vrednosti HQinh za decu i odrasle prelaze vrednost 1 ukazujući na neprihvatljiv rizik od izloženosti arsenu preko PM10 čestica iz zagađenog vazduha na svim razmatranim mernim stanicama. Neprihvatljiv karcinogeni rizik za decu je izračunat na stanici Bor-Jugopetrol, a za odrasle na stanicama Bor-Gradski park, Bor 1 i Bor-Jugopetrol. Dobijeni rezultati ukazuju na preku potrebu preduzimanja mera u cilju smanjenja emisije arsena u vazduh u Boru. VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beograd

Valproic acid (VPA) is antiepileptic drug with a long history of clinical use, increasingly applied in the treatment of various diseases (bipolar disorder, migraine prophylaxis, etc). Due to significant inter-individual differences VPA concentration is often measured in the purpose of therapeutic drug monitoring (TDM) (1). Acute poisonings with this drug represent a significant problem. According to the American Association of Poison Control Centers, there has been VPA poisoning incidence increase in the last 20 years. Reports from the National Poison Control Center in Belgrade list VPA as one of the three most common causes of antiepileptic drugs intoxications (2). This paper aimed to develop a modern analytical method for VPA quantification in patient plasma. UPLC/MS method with fast and simple sample preparation has been validated. After protein precipitation, VPA was extracted from 100 μL plasma using HLB cartridges. Caprylic acid solution was used as internal standard. Chromatographic separation was achieved on C18 column (1.8 μm, 2.1 X 150 mm) with gradient elution at constant mobile phase flow. Good peak resolution was achieved (Rt VPA - 4.73 min, Rt ISTD - 4.94 min). Validation was performed according European Medicines Agency recommendations. Based on statistical analysism it was shown that the method is precise, accurate, specific, sensitive and linearity is confirmed in a wide range of concentrations (1-250 mg / L). Advantages of this method are simple preparation procedure from a small amount of sample, without prior derivatization and short duration of analysis, which fully satisfies the needs of TDM and urgent toxicological analyses. Valproinska kiselina (VK) je lek iz grupe antiepileptika sa dugom istorijom kliničke upotrebe, koji se, osim u terapiji epilepsije, poslednjih decenija sve više koristi u terapiji različitih bolesti (bipolarni poremećaj, profilaksa migrene itd). Zbog značajnih interindividualnih varijacija, koncentracija VK se često određuje u svrhe terapijskog praćenja leka (TDM – Therapeutic Drug Monitoring) (1). S druge strane, akutna trovanja ovim lekom predstavljaju značajan problem. Prema podacima Američkih centara za kontrolu trovanja došlo je do povećanja incidence trovanja VK u poslednjih 20 godina, dok izveštaji Nacionalnog centra za kontrolu trovanja u Beogradu navode VK kao jedan od tri najčešća uzročnika trovanja kada su u pitanju intoksikacije antiepilepticima (2). Cilj ovoga rada je razvoj savremene analitičke metode za određivanje koncentracije VK u plazmi pacijenata. Validovana je UPLC/MS metoda koja podrazumeva brzu i jednostavnu pripremu uzorka. Nakon precipitacije proteina, izvršena je ekstrakcija iz 100 μL plazme uz pomoć HLB kertridža. Kao interni standard korišćen je rastvor kaprilne kiseline. Hromatografsko razdvajanje je postignuto na C18 koloni (1,8 μm, 2,1 X 150 mm) gradijentnim eluiranjem pri konstantnom protoku mobilne faze. Postignuta je dobra rezolucija pikova (Rt VK - 4,73 min, Rt ISTD - 4,94 min). Validacija je izvedena prema preporukama Evropske agencije za lekove, a na osnovu statističke analize je pokazano da je metoda precizna, tačna, specifična, osetljiva i potvrđena je linearnost u širokom opsegu koncentracija (1-250 mg/L). Prednosti ove metode su jednostavan način pripreme iz male količine uzorka, bez prethodne derivatizacije, i kratko vreme trajanja analize, što u potpunosti zadovoljava potrebe TDM-a i urgentnih toksikoloških analiza. VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beograd

Opioids are a wide group of natural, semi-synthetic and synthetic substances, used in the pharmacotherapy of painful conditions. However, due to their psychoactive properties, they are often abused. Immunochromatographic test panels are used for substance abuse monitoring and are quick, simple and based on the principle of competitive binding. Main disadvantage of immunochromatographic analysis is cross-reactivity, because of sufficient specificity of test antibodies for the analyte of interest. This study aimed to examine the effect of codeine-based OTC preparation (Caffetin®) on false positive results of preliminary opiate urineanalysis, and determine the time period during which these results may occur. The study included two female healthy subjects, 23 and 24 years old. One of them administered double oral dose of Caffetin® (two tablets - total of 20 mg of codeine) and the other administred single oral dose of Caffetin® (one tablet - 10mg of codeine). Urine samples were collected for 48h. Analysis was performed by AmeritekOPI® monocomponent test strips and DOAMultiGnost 3 Test Panel® multicomponent test strips. The use of Caffetin® gave false positive results for opiates after 4,7h (Subject 1) and 3,3 h (Subject 2). The first negative result occurred after 39h (Subject 1) and 37,9h (Subject 2). After application of codeine-based OTC preparations, false positive results were obtained in less than 48h. Literature data indicate that positive results on opiates might occur 48h after consuming of codeine-based medication. Hence, it is necessary to carry out further research with aim to avoid doubts during interpretation of immunochromatographic test results. Opioidi predstavljaju široku grupu supstanci prirodnog, polusintetskog i sintetskog porekla, koje se osim primene u farmakoterapiji bolnih stanja, , često zloupotrebljavaju. Za kontrolu zloupotrebe koriste se imunohromatografske test trake, brza i jednostavna analiza zasnovana na principu kompetitivnog vezivanja. Glavni nedostatak im je pojava ukrštene reaktivnosti usled niske specifičnosti antitela za analit od interesa. Cilj ovog rada je bio ispitati uticaj primene OTC preparata koji sadrži kodein (Caffetin®) na pojavu lažno pozitivnih rezultata preliminarne imunohromatografske analize opijata u urinu i utvrditi vremenski period njihove pojave od trenutka primene analgetika. U istraživanju su učestvovale dve zdrave ženske osobe starosti 23 i 24 godine. Jedna ispitanica je primenila dozu koja sadrži 20 mg kodeina (2 tablete), a druga 10 mg kodeina (1 tableta). Uzorci urina su sakupljani tokom narednih 48 h i analiza je vršena pomoću dve vrste imunohromatografskih test traka: monokomponentnim AmeritekOPI ® i trokomponentnim DOAMultiGnost 3 Test Panel® . Primenom Caffetin® tableta dobijeni su lažno pozitivni rezultati na opijate prvi put nakon 4,7 h (Ispitanica 1) i 3,3 h (Ispitanica 2), a prvi negativan rezultat se javio posle 39 h (Ispitanica 1) i 37,9 h (Ispitanica 2). Utvrđeno je da se nakon primene OTC preparata sa kodeinom dobijaju lažno pozitivni rezultati na opijate u vremenskom periodu kraćem od 48 h. Imajući u vidu da literaturni podaci ukazuju na to da uzorak može biti pozitivan na opijate i do 48 h pri primeni kodeina, neophodno je sprovesti detaljnija ispitivanja kako bi ova pojava u manjoj meri dovodila do nedoumica prilikom tumačenju rezultata imunohromatografskih testova. VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beograd

Exposure to lead (Pb) and cadmium (Cd) poses risk to human health. It is known that these metals have toxic impact on male reproductive system, leading to physiological disorders and infertility. Limited data indicates the carcinogenic potential of Pb, while Cd has been recognized as carcinogen. Benchmark dose-effect modeling can be applied to data from human, animal and ecotoxicological studies with the aim to obtain Benchmark dose (BMD), starting point in human health risk assessment. The aim of this study was to use Benchmark modeling to determine the dose-effect relationship between Pb and Cd levels in tissues of testicular and prostate cancer patients and serum testosterone levels. The study was conducted at the Clinical Center of Serbia, and included 104 patients with prostate and testicular cancer. Cd and Pb levels (ng/g) were measured by atomic absorption spectrophotometry in isolated healthy surrounding and carcinoma-affected tissues. Testosterone levels (ng/mL) were measured using the chemiluminescence immunoassay (CLIA) method. Dose-effect modeling was performed using PROAST70.1 software with continuous data. The dose dependence was obtained between Cd levels in tumor tissue and testosterone levels (BMD: 0.0024 ng Cd/g, prostate cancer and 0.0038 ng Cd/g, testicular cancer). Dose dependence was obtained between Cd levels in healthy surrounding tissue and testosterone levels (BMD: 0.0092 ng Cd/g). No dose dependence was obtained when modeling Pb levels as a dose. The data from this study indicate a potential link between Cd and testosterone levels, i.e. potential association of Cd exposure with male reproductive health. Izloženost olovu (Pb) i kadmijumu (Cd) predstavlja rizik po zdravlje ljudi. Poznato je da ovi metali deluju toksično na muški reproduktivni sistem dovodeći do poremećaja fizioloških funkcija i neplodnosti. Ograničen broj studija ukazuje na kancerogeni potencijal Pb, dok je Cd poznatihumani karcinogen. Benchmark modelovanje odnosa doza-efekat se teoretski može primeniti na podacima iz humanih, animalnih i ekotoksikoloških studija, sa ciljem dobijanja Benchmark doze (BMD) kao polazne tačke u proceni rizika po zdravlje ljudi. Cilj ovog rada bio je da se Benchmark modelovanjem utvrdi odnos doza-efekat između nivoa Pb i Cd u tkivima karcinoma testisa i prostate pacijenata i nivoa testosterona u serumu. Studija je sprovedena na Kliničkom centru Srbije i uključila je 104 pacijenta sa karcinomom prostate i testisa. Nivoi Cd i Pb (ng/g) su izmereni metodom atomske apsorpcione spektrofotometrije u izolovanim zdravim okolonim i karcinomom zahvaćenim tkivima. Nivoi testosterona (ng/mL) su mereni pomoću metode direktnog kompetitivnog hemiluminiscentnog imunoeseja (CLIA). Modelovanje odnosa doza-efekat je vršeno pomoću PROAST 70.1 softvera (RIVM, Holandija) uz upotrebu kontinuiranih podataka. Dozna zavisnost je dobijena između nivoa Cd u tumorskom tkivu i nivoa testosterona gde je BMD vrednost iznosila 0,0024 ng Cd/g (karcinom prostate) i 0,0038 ng Cd/g (karcinom testisa). Dozna zavisnost je dobijena i za modelovanje odnosa nivoa Cd u zdravom tkivu i testosterona, sa BMD vrednošću 0,0092 ng Cd/g. Pri modelovanju nivoa Pb nije dobijena dozna zavisnost. Podaci ove studije ukazuju na potencijalnu vezu između nivoa Cd u tkivu i nivoa testosterona, ukazujući na efekte izloženosti ovom metalu na muško reproduktivno zdravlje. VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beograd

The aim of this investigation was to present data analysis on acute poisonings with fatal outcome in the Republic of Serbia in from 2010 to 2018, based on the published Annual reports of the National Poison Control Center of the Military Medical Academy (1). In the observed 9-year period, the most common cause of acute poisoning was alcohol (50%), followed by drugs (30.1%), while in the third and fourth place were psychoactive substances (7.1%) and gases 4%. Corrosive and pesticide poisoning was present in only 2% of the total number of examined patients per year. The most common reason for the hospitalization was due to drug poisoning (71%), corrosives (9%), pesticides (5%), psychoactive substances (4%), gases (4%) and other pathogens (7%). From 2010 to 2018, number of deaths due to acute poisoning ranged from 26 to 43 annually with an average value of 33. Of 290 deceased patients, 101 (34.9%) were of drug poisoning, 108 (38.5%) corrosives, 28 (9.8%) pesticides, 4 (1.4%) gases, 14 (4.6%) psychoactive substances and 37 (12.4%) other substances, predominantly alcohols and mushrooms. Combination of two or more drugs most often led to death (n=51), while among corrosives, hydrochloric acid was the most common (n=40). Of the pesticides, the most common were organophosphorus insecticides (n=14), while heroin was the most common psychoactive substance (n=7). The analyzed data indicated the importance of preventive measures that need to be carried out in our country to reduce the number of acute poisonings, especially the most severe forms that lead to death. Cilj ovog rada bio je da se prikaže analiza podataka o akutnim trovanjima sa smrtnim ishodom u Republici Srbiji u periodu od 2010. do 2018. godine na osnovu publikovanih Godišnjaka Nacionalanog centra za kontrolu trovanja Vojnomedicinske akademije (1). U posmatranom devetogodišnjem periodu najčešći uzročnik akutnih trovanja je alkohol (50%), zatim lekovi (30,1%), dok su na trećem i četvrtom mestu psihoaktivne supstance (7,1%) i gasovi 4%. Samo oko 2% od ukupnog broja pregledanih pacijenata godišnje su slučajevi trovanja korozivima i pesticidima. Najčešći razlog hospitalizacije je usled trovanja lekovima (71%), zatim korozivima (9%), pesticidima (5%), psihoaktivnim supstancama (4%), gasovima (4%) i drugim uzročnicima (7%). Od 2010. do 2018. godine broj letalnih ishoda usled akutnog trovanja se kretao od 26 do 43 slučaja godišnje sa prosečnom vrednošću od 33 slučaja po godini. Od 290 preminula pacijenta, 101 (34,9%) slučaj je bilo trovanje lekovima, 108 (38,5%) korozivima, 28 (9,8%) pesticidima, 4 (1,3%) gasovima, 14 (4,6%) psihoaktivnim supstancama i 37 (12,4%) ostalim supstancama, dominantno alkoholima i gljivama. Kombinacija dva i više lekova je najčešće dovela do smrtnog ishoda (n=51), dok je među korozivima, najzastupljenija bila hlorovodonična kiselina (n=40). Od pesticida kao uzročnika akutnih trovanja sa smrtnim ishodom najzastupljeniji su organofosforni insekticidi (n=14), a prema broju smrtnih ishoda od psihoaktivnih supstanci najviše je zastupljen heroin (n=7). Analizirani podaci ukazuju na značaj preventivnih aktivnosti koje je u našoj zemlji potrebno sprovesti kako bi se smanjio broj akutnih trovanja, a time i onih najtežih oblika koji dovode do smrtnog ishoda. VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beograd

Adverse outcome pathways (AOPs) represent a tool in toxicology, introduced in 2010 by scientists from the US Environmental Protection Agency as a framework to support ecotoxicological research and risk assessment. In 2012, Organization for Economic Cooperation and Development initiated an international AOPs development program. Since then, AOPs have been promoted as useful tool in health risk assessment, development of Integrated Approaches to Testing and Assessment and for developing novel animal-free test methods (1,2). AOPs provide structured frameworks for collecting, organizing and evaluating existing toxicological knowledge on mechanistic pathways. AOPs describe biologically plausible chains of events, linking a molecular initiating event to key events at different levels of biological organization and, finally, to an adverse outcome. Not being stressor-specific, the ultimate utility of AOPs should be to predict adverse effects of any type of stressor, including chemicals, nanomaterials, pharmaceuticals, etc. with unknown toxic effects for which the toxicological mechanisms are known or can be tested. AOPs have been suggested as structured basis for predicting drug-induced liver injury (steatosis, fibrosis, cholestasis) and for developing in silico and in vitro methods for screening, as well as targeted methods for pre-clinical testing to assess liver toxicity, common reason for withdrawing pharmaceuticals from the market. AOPs have also been proposed as useful framework for method development and integration of in vitro data in personalized cancer therapy. In conclusion, AOPs concept plays an important role in the 21 st century toxicology paradigm supporting predictive toxicology with alternative assays and reduction of the need for animal use. Put štetnog ishoda (engl. adverse outcome pathway, AOP) predstavlja alatku u toksikologiji prvi put uvedenu 2010. godine od strane naučnika Američke agencije za zaštitu životne sredine sa ciljem podrške istraživanjima u ekotoksikologiji. Već 2012. godine Organizacija za ekonomsku saradnju i razvoj pokrenula je međunarodni program razvoja AOP. Od tada, AOP je promovisan kao koristan pristup u proceni rizika po zdravlje ljudi, razvoju novih metoda i integrisanih pristupa testiranju i evaluaciji štetnih efekata (1,2). AOP daje struktuirani okvir za prikupljanje, organizaciju i procenu postojećeg znanja o mehanističkim putevima u toksikologiji. AOP opisuje biološki verovatan lanac događaja povezujući inicijalni molekularni događaj, preko tzv. ključnih događaja na različitim nivoima biološke organizacije, sa štetnim efektom. AOP nije specifičan i kao takav, treba da posluži za predviđanje štetnih efekata različitih stresora, kao npr. hemikalija, nanomaterijala, lekova i drugih, sa nepoznatim štetnim efektom, ali za koje su poznati ili se mogu ispitati mehanizmi toksičnosti. Opisani su AOP u cilju predviđanja lekovima indukovanih oštećenja jetre (steatoza, fibroza, holestaza), kao i u cilju razvoja in silico i in vitro metoda za skrining i pretkliničko ispitivanje ovih efekata, koji su jedan od čestih razloga povlačenja lekova sa tržišta. AOP je predložen i kao koristan okvir za razvoj metoda i integraciju in vitro podataka u personalizovanu terapiju karcinoma. Konačno, AOP koncept igra važnu ulogu u toksikologiji 21. veka, koja podržava prediktivnu toksikologiju sa altentativnim metodama i smanjenjem potrebe za eksperimentalnim životinjama. VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beograd

The aim of this study was to: (1) examine subacute toxicity of bis (2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and bisphenol A (BPA) mixture in rats and compare it with individual substance effects; (2) investigate the mechanisms of toxicity on critical target organ, testes (in vivo/in silico study); (3) examine multibiotic ability to mitigate mixture toxicity. Male rats were divided into groups (n = 6): (1) Control; (2) P (probiotic (8.78*10 8 CFU/kg bw/day)); (3) DEHP (50 mg/kg bw/day); (4) DBP (50 mg/kg bw/day); (5) BPA (25 mg/kg bw/day); and (6) MIX (50 mg/kg bw/day DEHP + 50 mg/kg bw/day DBP + 25 mg/kg bw/day BPA) (7) MIX + P. In silico toxicogenomic analysis was performed by Comparative Toxicogenomic Database (CTD), Citoscape software and ToppGene Suite portal. MIX led to significant changes in tissue structure (liver, kidney, spleen and testis), biochemical parameters and testosterone level of rats compared to the control group and individual substances. In silico analysis revealed 20 genes associated with DEHP/DBP/BPA and male reproductive system disorders, while the most probable mechanisms included metabolism, aryl hydrocarbon receptor pathway, apoptosis, and oxidative stress. Oxidative stress was confirmed in vivo, and changes in parameters in testicular tissue homogenates were most pronounced or present only in MIX group. Probiotic annulled/mitigated changes in biochemical, hematological, and oxidative stress parameters, relative liver mass, food consumption, and organ pathohistology. Hence, the obtained results indicate the possibility of future considerations of protective probiotic effects against phthalates and BPA mixture toxicity. Cilj ove studije bio je: (1) ispitati subakutnu toksičnost smeše bis (2-etilheksil) ftalata (DEHP), dibutil ftalata (DBP), bisfenola A (BPA) na pacovima i uporediti je sa efektima pojedinačnih supstanci; (2) istražiti mehanizme toksičnosti na kritičnom ciljnom organu, testisima (in vivo/in silico studija); (3) ispitati sposobnost višekomponentnog probiotika da ublaži toksičnost smeše. Mužjaci pacova podeljeni su u grupe (n = 6): (1) Kontrola; (2) P (probiotik (8.78 * 108 CFU/kg/day)); (3) DEHP (50 mg/kg t.m/dan); (4) DBP (50 mg/kg t.m/dan); (5) BPA (25 mg/kg t.m/dan); i (6) MIX (50 mg/kg t.m/dan DEHP + 50 mg/kg t.m/dan DBP + 25 mg/kg t.m/dan BPA) (7) MIX + P. In silico toksikogenomička analiza sprovedena je Komparativnom toksikogenomičkom bazom podataka (CTD), Citoscape softverom i ToppGene Suite portalom. Smeša je dovela do značajnih promena u strukturi tkiva (jetra, bubreg, slezina i testis), biohemijskim parametrima i nivou testosterona pacova u poređenju sa kontrolnom grupom i pojedinačnim supstancama. In silico analizom otkriveno je 20 gena povezanih sa smešom DEHP/DBP/BPA i poremećajima muškog reproduktivnog sistema, dok su najverovatniji mehanizmi uključili metabolizam, molekularni put povezan sa receptorom za aromatične ugljovodinike, apoptozu i oksidativni stres. Oksidativni stres potvrđen je in vivo, a promene u parametrima u homogenatu tkiva testisa bile su najizraženije ili prisutne samo u MIX grupi. Probiotik je otklonio ili ublažio promene u biohemijskim, hematološkim, i parametrima oksidativnog stresa, kao i relativnoj masi jetre, unosu hrane i patohistološkim nalazima izazvanim smešom ispitivanih supstanci. Dobijeni rezultati ukazuju na mogućnost budućih razmatranja protektivnih efekata probiotika protiv toksičnosti smeše ftalata i BPA. VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beograd

PM10 particles present in excessive concentrations in polluted air can negatively affect respiratory and cardiovascular system, whereas lead exposure shows adverse effects on renal, hematological, immunological, reproductive and neurological system, especially in children (1). This study was carried out to assess children’s exposure to PM 10 and lead through the air in critical districts of Serbia. Mean yearly concentrations of PM10 and lead were used from reports of the Serbian Enviromental Protection Agency, for selected measuring sites in the cities of Subotica, Smederevo, Bor, Valjevo and Kraljevo. Measuring sites were selected based on air quality (over-polluted air) and being close to places where children spend their time during the day. The US EPA method was used to assess health risk, which classifies risk as acceptable (≤1) or unacceptable (>1) based on hazard quotient (HQ) and hazard index (HI) values (2). HQ for PM10 particles was higher than 1 in all critical districts, indicating risk as unacceptable. Values of HI for lead were lower than 1 in all critical districts, indicating risk as acceptable. Results are showing that actions for reduction of air pollution in Serbia should be taken due to obtained results for particulate matter and lead. PM10 čestice prisutne u prekomernim koncentracijama u zagađenom vazduhu ispoljavaju štetne efekte na respiratorni i kardiovaskularni sistem, dok olovo negativno utiče i na renalni, hematopoetski, endokrini, imunološki, reproduktivni i nervni sistem, naročito kod dece (1). Cilj ovog rada bio je da se proceni izloženost dece PM10 česticama i olovu putem zagađenog vazduha u kritičnim područjima Srbije. Vrednosti prosečnih godišnjih koncentracija PM 10 čestica i olova su preuzete iz godišnjih izveštaja Agencije za zaštitu životne sredine, za odabrane merne stanice u gradovima Subotica, Smederevo, Bor, Valjevo i Kraljevo. Kriterijum za izbor područja, odnosno mernih stanica, bio je kvalitet vazduha (prekomerno zagađen vazduh) i blizina mesta gde deca provode značajan deo vremena. Zdravstveni rizik je procenjen metodologijom koju preporučuje Američka agencija za zaštitu životne sredine. Na osnovu vrednosti količnika hazarda (HQ) i indeksa hazarda (HI) rizik se klasifikuje kao prihvatljiv (≤1) ili neprihvatljiv (>1) (2). HQ za PM10 čestice prelazi vrednost 1 u svim razmatranim područjima, ukazujući na neprihvatljiv rizik dok su vrednosti HI za olovo manje od 1 ukazujući na prihvatljiv rizik u svim područjima. Dobijeni rezultati ukazuju na potrebu preduzimanja mera u cilju smanjenja zagađenja vazduha u Republici Srbiji na osnovu izračunatog zdravstvenog rizika od izloženosti suspendovanim česticama i olovu. VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beograd

Amphetamine is a potent stimulant of central nervous system and one of the most often abused substances. Immunochromatographic test panels for preliminary urineanalysis are used to track its abuse. Immunochromatographic analysis is quick, simple and based on the principle of competitive binding. Its main disadvantage is cross reactivity - tendency of antibodies to bind structurally similar compounds, including pseudoephedrine. This study aimed to examine the effect of pseudoephedrine-based OTC preparations on the occurrence of false-positive results of preliminary amphetamine urineanalysis and determine the time period during which these results may occur. The study included two subjects. TylolHot® was used for two days, while, on the first day, single dose was administered. On the second day, preparation was administered according to the dosing regimen recommended by the manufacturer (three times a day). Urine samples were collected for three consecutive days. Analysis was performed by immunochromatographic test strips "DIAQUICK" Multi-Drug Test Panels. TylolHot® use led to false positive results for amphetamine 3.75 h after single administration, and lasted for 27 h with repeated administration. After the application of the tested preparation, false positive results on amphetamine were obtained in different time periods, which depended on the intra- and interindividual variations, as well as the dosing regimen. Although test strips are used for quick preliminary analysis, it is necessary to check the results via confirmation methods (gas or liquid chromatography coupled to mass spectrometry). The obtained results are significant during routine testing of patients, employees, students, athletes and members of the army. Amfetamin je snažan stimulans centralnog nervnog sistema i jedna od supstanci koja se najčešće zloupotrebljavaju. Za praćenje njegove zloupotrebe koriste se imunohromatografske test trake za preliminarnu analizu urina. Imunohromatografska analiza je brza i jednostavna metoda koja se zasniva na principu kompetitivnog vezivanja. Njen glavni nedostatak je unakrsna reaktivnost – sklonost antitela da vezuju strukturno slična jedinjenja, između ostalih i pseudoefedrin. Cilj ovog rada bio je ispitati uticaj primene OTC preparata na bazi pseudoefedrina na pojavu lažno pozitivnih rezultata preliminarne analize amfetamina u urinu i utvrditi vremenski period pojave ovih rezultata od trenutka primene preparata. Ispitivanje je uključivalo dva ispitanika. Tokom dva dana korišćen je preparat TylolHot® , pri čemu je prvi dan primenjena jedna doza, a drugi dan se preparat primenjivao prema režimu doziranja preporučenom od strane proizvođača (tri puta dnevno). Uzorci urina sakupljani su tokom tri uzastopna dana, a analiza je izvršena imunohromatografskim test trakama "DIAQUICK" Multi-Drug Test Panels. Dobijeni su lažno pozitivni rezultati na amfetamin već u periodu od 3,75 h nakon jednokratne primene TylolHot ® preparata, i trajali su tokom 27 h pri višekratnoj primeni. Utvrđeno je da se nakon primene TylolHot® preparata u različitim vremenskim periodima mogu dobiti lažno pozitivni rezultati, što zavisi od intra- i interindividualnih varijacija i režima doziranja. Iako se test trake koriste za brzu preliminarnu analizu, neophodno je potvrditi rezultate konfirmativnim metodama (gasna ili tečna hromatografija spregnuta sa masenom spektrometrijom). Dobijeni rezultati su značajni prilikom rutinskih testiranja pacijenata, zaposlenih, učenika, sportista i pripadnika vojske. VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beograd

The atypical antipsychotic clozapine (CLZ) is primarily used for the treatment- resistant schizophrenia. Due to low therapeutic index and high pharmacokinetic variability, therapeutic drug monitoring (TDM) is highly recommended (1). The aim of this retrospective study was to analyze TDM data of CLZ and its active metabolite norclozapine (NCLZ) in adult patient with schizophrenia. The study included CLZ TDM data obtained from 69 patients (22- 67 years) treated at the Clinic for Psychiatry, Clinical Center of Serbia, while NCLZ data were available from 43 patients. Serum concentrations were determined at the Institute of Forensic Medicine, Belgrade, Serbia using liquid chromatography with tandem mass spectrometry (LC‐MS/MS). Statistical analysis was performed by SPSS software® (version 18). The daily doses of CLZ ranged between 37.5 and 600 mg. The mean value of CLZ and NCLZ levels were 0.285 ± 0.174 mg/L and 0.189 ± 0.132 mg/L, respectively. 73.06% and 26.83% of measured CLZ and NCLZ concentrations were outside reference range (mostly below), respectively. Significant positive correlation (p

The aim of this study was to evaluate the awareness of livestock breeders on the used veterinary drugs in order to assess potential environmental contamination in the region of Sjenica. Veterinary drugs can enter the environment mostly due to widespread usage, but also as metabolites eliminated from the organisms. In order to evaluate the awareness of livestock breeders, a survey questionnaire was used. Questions were related to the most frequently used veterinary drugs without the supervision of a veterinary medical doctor. The obtained data show that the awareness of domestic animal breeders on the use of veterinary drugs is very low in the region of Sjenica. The most commonly used veterinary medicines were antibiotics, streptomycin, and benzylpenicillin-procaine, antihelmintic, albendazole. Unexpectedly, the animal breeders identified formaldehyde as veterinary medicine and used it as a disinfectant in poultry raising. The results also show that breeders frequently treat animals with drugs on their own, without control by veterinary medical doctors. Because of the wide use of veterinary medicines in the region of Sjenica, it monitoring of the environmental concentration of streptomycin, benzylpenicillin-procaine, and albendazole, as well as metabolites in soil and water should be recommended. Moreover, human exposure to these veterinary medicines could occur because of the abuse of veterinary medicines, no consultations with veterinary medical doctors, and non-proper handling of waste from animals. Veterinarski lekovi dospevaju u životnu sredinu najčešće usled neadekvatnog odlaganja otpada, ali i kao metaboliti iz organizma životinja. Cilj studije je bio procena nivoa svesti uzgajivača stoke o upotrebi veterinarskih lekova u regionu Sjenice sa ciljem procene potencijalne kontaminacije životne sredine. Za procenu nivoa svesti uzgajivača stoke korišćen je anketni upitnik. Pitanja iz upitnika su se odnosila na najčešće korišćene veterinarske lekove i korišćenje bez nadzora veterinara. Dobijeni podaci pokazuju da je nivo svestu uzgajivača stoke u regionu Sjenice nizak jer koriste veterinarske lekove bez nadzora veterinara. Najčešće koriste antibiotike, streptomicin i benzoil-penicilin, antihelmintik – abendazol i, iznenađujuće, koriste formaldehid za dezinfekciju prostorija za smeštaj životinja, pri čemu ga smatraju veterinarskim lekom. Zbog rasprostranjene upoutrebe veterinarskih lekova u regionu Sjenice od strane uzgajivača stoke, a bez kontrole veterinara preporučuje se monitoring streptomicina, benzoilpenicilina i abendazola kao i njihovih metabolita u životnoj sredini, zemljištu i vodi. Potrebno je preduzeti dodatne mere opreza da zbog niskog nivoa svesti ne bi došlo do izloženosti ljudi ovim veterinarskim lekovima i njihovim metabolitima naročito zbog neadekvatnog tretiranja stajnjaka i drugog otpada. VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beograd

Polluted air is significant factor with a negative impact on human health. Solving the problem of polluted air requires involvement of the health system and health workers, among whom pharmacists in public pharmacies can stand out as the most accessible health workers with the highest knowledge in the field of toxicology. Considering the indisputable role of pharmacists in improving health and disease prevention, raising public awareness of air pollution health impact and advising patients on activities in case of air pollution, pharmacists would contribute to maintaining health, reducing the burden on the health system and its efficiency and sustainability. The pharmaceutical profession can make a significant contribution to combating the impact of air pollution on human health by increasing the availability of guidelines in the case of polluted air, increasing the availability of air quality monitoring tools, strengthening educational capacity models, participating in regulatory frameworks and improving funding for pharmaceutical services. In order for these responsibilities to be fully incorporated into pharmaceutical practice, it is necessary to: implement education in the field of toxicology, both at basic and higher levels of study in order to develop the necessary competencies; increase public awareness of the health consequences of air pollution, as well as the new roles of pharmacists; develop appropriate guidelines, regulatory and financial support as well as screening tools. With this in mind, the role of pharmacists in reducing the impact of air pollution on human health should be recognized and developed in order to protect human health. Zagađen vazduh predstavlja značajan faktor koji ima negativan uticaj na zdravlje ljudi. Rešavanje problema zagađenog vazduha zahteva uključivanje zdravstvenog sistema i zdravstvenih radnika, među kojima se mogu istaći farmaceuti u javnim apotekama kao najdostupniji zdravstveni radnici, sa najvišim znanjima iz oblasti toksikologije. Imajući u vidu neospornu ulogu farmaceuta u unapređenju zdravlja i prevenciji bolesti, podizanjem svesti javnosti o uticaju zagađenja vazduha na zdravlje ljudi i davanjem saveta pacijentima o aktivnostima u slučaju zagađenja vazduha, farmaceuti bi doprineli očuvanju zdravlja, smanjenju opterećenja zdravstvenog sistema i njegovoj efikasnosti i održivosti. Farmaceutska profesija može značajno doprineti suzbijanju uticaja zagađenja vazduha na zdravlje ljudi i to: povećanjem dostupnosti smernica u slučaju zagađenog vazduha, povećanjem dostupnosti alata za monitoring kvaliteta vazduha, jačanjem obrazovnih kapaciteta, učestvovanjem u donošenju regulatornih okvira i poboljšanjem modela finansiranja farmaceutskih usluga kako bi se obezbedila održivost. Da bi navedene odgovornosti bile u potpunosti inkorporirane u farmaceutsku praksu, potrebno je: implementirati edukaciju iz oblasti toksikologije, kako na osnovnim tako i na višim nivoima studija kako bi se razvile neophodne kompetencije; povećati svest javnosti o zdravstvenim posledicama zagađenja vazduha, kao i o novim ulogama farmaceuta; razviti odgovarajuće smernice, regulatornu i finansijsku podršku kao i alate za skrining. Imajući navedeno u vidu, uloga farmaceuta u smanjenju uticaja zagađenja vazduha na zdravlje ljudi treba biti prepoznata i razvijena sa ciljem očuvanja zdravlja. VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beograd

Organic solvents are still widely used in various industries and considered the most common chemicals associated with liver injury in workers. For research into the relationships between these chemicals and genes, interactions among chemicals, molecular pathways and biological processes, a significant place in toxicity testing has been taken by in silico methodologies. This study aims to provide evidence for the involvement of a selected mixture of organic solvents (toluene, styrene, ethanol) in liver disease development and show the potential of in silico toxicogenomic data-mining in determining possible mechanisms of mixture toxicity. The Comparative Toxicogenomics Database (CTD), GeneMania and ToppGene Suite were used for data-mining. The results showed that there were 17 genes connected with liver injury common for all the tested solvents. Co-expression (61.73%) was the most prominent interaction between the genes, while physical interactions were present at 14.56%, co-localization at 12.54% and interactions predicted by the server at 6.62%. Gene ontology analysis revealed biological processes affected by the investigated mixture (reactive oxygen species metabolic and biosynthetic process, response to oxidative stress, and response to organic cyclic compound). Oxidative stress response, antioxidant and oxidoreductase activity, vitamin B12 metabolism were noted as the key molecular pathways contributing to liver disease development. Our results emphasize the role of oxidative stress as one of the mechanisms of organic solvents' mixture toxicity and provide new insights into molecular mechanisms involved in hepatotoxicity. Organski rastvarači se još uvek široko koriste u raznim industrijama i smatraju se najčešćim hemikalijama povezanim sa oštećenjem jetre kod radnika. Za istraživanje odnosa između ovih hemikalija i gena, interakcija među hemikalijama, molekularnih puteva i bioloških procesa, značajno mjesto pripada i in silico metodologijama. Cilj ove studije je da pruži dokaze za povezanost odabrane smeše organskih rastvarača (toluen, stiren, etanol) u razvoju bolesti jetre, i da pokaže potencijal in silico toksikogenomičke analize podataka u određivanju mogućih mehanizama toksičnosti smješe. Za prikupljanje podataka korišteni su Comparative Toxicogenomics Database (CTD), GeneMania i ToppGene Suite. Rezultati ove analize su pokazali da postoji 17 gena povezanih s oštećenjem jetre zajedničkih za sva tri navedena rastvarača. Koekspresija (61,73%) bila je najistaknutija interakcija između gena, dok su fizičke interakcije bile prisutne sa 14,56%, kolokalizacije sa 12,54%, a interakcije predviđene od strane servera sa 6,62%. Analiza ontologije gena izdvojila je biološke procese na koje utiče ispitivana smeša (metabolički i biosintetski proces reaktivnih kiseonikovih vrsta, odgovor na oksidativni stres i odgovor na organska ciklična jedinjenja). Odgovor na oksidativni stres, aktivnost antioksidanata i oksidoreduktaze, i metabolizam vitamina B12 su navedeni kao ključni molekularni putevi koji dobrinose razvoju bolesti jetre. Rezultati ovog rada naglašavaju ulogu oksidativnog stresa kao jednog od mehanizama toksičnosti smeše organskih rastvarača i daju novi uvid u molekularne mehanizme uključene u hepatotoksičnost. VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beograd

Lead (Pb) is one of the most important toxic metals without known physiological role. Recent data indicate that any exposure, even low, can be harmful. Therefore, safe blood lead levels, as well as tolerating daily intake, have not been identified. In adults, the most sensitive effect is increase in systolic blood pressure, while in children, the most sensitive effect is on cognition. Therefore, the aim of this study was to examine the effects of low lead doses on the central nervous and cardiovascular system in a rat model. The study was conducted on Wistar rats (n = 42; 7 groups) treated for 28 days, with increasing doses of 0.1; 0.5; 1; 3; 7; 15 mgPb/kg b.w./day to simulate real exposure. After the sacrifice, the brain and heart were isolated, in which the parameters of oxidative status, bioelements and lead levels were determined. Benchmark modelling of the dose-effect relationship was performed using PROAST 70.1 software (RIVM, Netherlands). The obtained results indicate that lead leads to the induction of oxidative stress and dishomeostasis of bioelements. The lowest value of the Benchmark dose (BMD) was obtained for increase the total oxidative status in the brain (4.49e-06 mgPb/kg/b.w./day), which is the most sensitive effect. In the case of heart, the most sensitive effect was increase in malondialdehyde (BMD: 0.000248 mgPb/kg/b.w./day). Obtained results indicate that low lead doses have toxic effects on heart and brain. Obtained BMD may be useful in assessing human health risk of low lead dose exposure. Olovo (Pb) je jedan od najznačajnijih toksičnih metala bez poznate fiziološke uloge u organizmu. Novija istraživanja ukazuju da potencijalno svaka izloženost olovu, čak i niskim dozama, može biti štetna, te tolerišući dnevni unos, kao ni bezbedan nivo u krvi, nisu utvrđeni. Kod odraslih, kao najosetljiviji efekat izdvaja se povećanje sistolnog krvnog pritiska, dok je kod dece to poremećaj kognicije. Imajući navedeno u vidu, cilj ove studije bio je da se na animalnom modelu ispita uticaj niskih doza olova na centralni nervni i kardiovaskularni sistem, koji su do sada identifikovani kao najosetljiviji na dejstvo olova, i odrede Benchmark doze (BMD). Studija je sprovedena na modelu Wistar pacova koji su podeljeni u 7 grupa tretiranih tokom 28 dana rastućim dozama olova 0, 0,1; 0,5; 1; 3; 7; 15 mg Pb/kg t.m./dan kako bi se simulirala realna izloženost. Nakon žrtvovanja pacova, izolovani su mozak i srce u kojima su određeni olovo, bioelementi i parametri oksidativnog statusa. Benchmark modelovanje odnosa doza-efekat vršeno je pomoću PROAST 70.1 softvera (RIVM, Holandija). Dobijeni rezultati ukazuju da olovo dovodi do indukcije oksidativnog stresa i poremećaja homeostaze bioelemenata. Najniža BMD dobijena je za povećanje totalnog oksidativnog statusa u mozgu (4,49e-06 mg Pb/kg t.m./dan), što predstavlja najosetljiviji efekat, a u srcu je to povećanje koncentracije malondialdehida (BMD: 0,000248 mg Pb/kg t.m./dan). Dobijeni rezultati ukazuju da i niske doze olova mogu ispoljiti toksične efekte na srce i mozak, a dobijene BMD su od značaja za procenu rizika olova po zdravlje ljudi. VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beograd