Suchergebnisse

Polybrominated diphenyl ethers (PBDEs) represent group of persistant organic chemicals (POPs), usually used as flame retardant additives in a variety of matherials and commercial products. Since 2009, PBDEs have been placed on the list of POPs chemicals, covered by Stockholm convention which is aimed to limit or ban production, use, emission, import and export of persistent organic pollutants, due to human health and environmental protection. Predominant routes of human exposure by PBDEs are ingestion by food, inhalation or dermal. Based on experimental studies, targets for PBDEs toxicity are nervous system, liver, thyroid gland and development. According to International Agency for Research on Cancer (IARC) PBDEs are not classified as a carcinogens, whereas according to Environmental Protection Agency (EPA) only deca BDE is classified as possible human carcinogen. So far, PBDEs have not been incoporated in national legislative framework. There are no data on environmental contamination, occupational exposure and exposure of general population. Therefore, placing the data on PBDEs in the focus of publics could contribute to the process of risk characterisation, and give directions for risk management in the Republic of Serbia. ; Polibromovani difeniletri (PBDEs) su hemikalije koje se dodaju različitim proizvodima kojima smo okruženi u svakodnevnom životu da bi usporili i/ili sprečili izbijanja požara. Polibromovani difeniletri su 2009. godine pridruženi listi perzistentnih organskih polutanata (POPs) usvojenoj Stokholmskom konvencijom čiji je cilj da ograniči ili zabrani proizvodnju, upotrebu, emisiju ili uvoz i izvoz toksičnih supstanci označenih kao POPs radi zaštite zdravlja ljudi i životne sredine. Do ekspozicije ljudi PBDEs može doći ingestijom, inhalacijom, dermalno. Eksperimentalne studije ukazuju da PBDEs najznačajnije toksične efekte ispoljavaju na jetru, štitnu žlezdu, nervni sistem, rast i razvoj. Međunarodna agencija za istraživanje karcinoma (IARC) ne klasifikuje PBDEs kao karcinogene za ljude, a Američka agencija za zaštitu životne sredine (EPA) klasifikuje samo dekaBDE kao moguć karcinogen za ljude. U našoj zemlji PBDEs nisu inkorporirani u nacionalnu regulativu, nema podataka o nivou zagađenja životne sredine, o sadržaju ovih jedinjenja u radnom okruženju i ekpoziciji opšte populacije, stoga bi saznanja u ovoj oblasti doprinela procesu evaluacije i karakterizacije rizika, ali i dala smernice za upravljanje rizikom PBDEs hemikalijama u Republici Srbiji.

Smoked meat and smoked meat products represent a significant part of the human diet in Serbia. The process of smoking, i.e. wood combustion, is one of the most important sources of polycyclic aromatic hydrocarcarbons (PAHs). Considering the carcinogenic and mutagenic properties of some PAHs, these compounds have been in the spotlight of scientific interest. The EFSA (European Food Safety Authority) Panel on Contaminants in the Food Chain (CONTAM Panel) reviewed the available data on occurrence and toxicity of PAHs in food. In 2008, the CONTAM Panel concluded that benzo[a]pyrene is not a suitable indicator for the occurrence of PAHs in food. Based on the currently available data relating to occurrence and toxicity, the CONTAM Panel concluded that the sum of benzo[a]pyrene, chrysene, benz[a]anthracene and benzo[b]fluoranthene (PAH4) are the most suitable indicators of PAHs in food. These proposals have become part of the legislation both of EU and Serbia. From 1st September 2014, maximum residue limits (MRL) both for benzo[a]pyrene (2 μg/kg) and sum of PAH4 compounds (12 μg/kg), in smoked meat and meat products, were defined by the legislation of Serbia, which is in accordance with EU regulation. In this paper, the method has been developed for the determination of benzo[a]pyrene, chrysene, benz[a]anthracene and benzo[b]fluoranthene (PAH4 compounds) in smoked meat and smoked meat products. Accelerated solvent extraction (ASE) was used for extraction of lipids and lipophilic compounds. Solid Phase Extraction (SPE) was used in order to remove lipids from analysed samples. High-performance liquid chromatographic with fluorescence detection (HPLC-FL) was applied for identification and quantification of benzo[a]pyrene, chrysene, benz[a]anthracene and benzo[b]fluoranthene. Different conditions of HPLC-FL analysed were applied (mobile phase, HPLC column, oven temperature, flow) in order to achieve optimal conditions for qualitative and quantitative analysis of PAH4 compounds. ; Dimljeno meso i proizvodi od mesa zauzimaju važno mesto u ishrani stanovništva u Srbiji. S obzirom, da tokom dimljenja tj. procesom sagorevanja drveta nastaju policiklični aromatični ugljovodonici (Polycyclic Aromatic Hydrocarbons, PAH), koji su klasifikovani kao karcinogena i mutagena jedinjenja, proučavanje ovih jedinjenja uvek zaokuplja pažnju javnosti. Na osnovu podataka, koji su rezultat novih bioloških i toksikoloških naučnih istraživanja, evropska naučna komisija o zagađivačima u lancu ishrane je u junu 2008. godine predložila da se suma sadržaja benzo[a]pirena, benzo[a]antracena, benzo[b]fluorantena i hrizena, tj. PAH4 jedinjenja koristi kao marker prisustva drugih PAH jedinjenja u različitoj hrani. Ovi predlozi postali su deo zakonske regulative, kako Evropske unije, tako i Srbije. Zakonska regulativa Srbije, koja je u saglasnosti sa propisima EU, od 1. septembra 2014. godine definiše maksimalno dozvoljenu količinu (MDK) za sumu sadržaja PAH4 jedinjenja (12 μg/kg), kao i za sadržaj benzo[a]pirena (2 μg/ kg) u dimljenom mesu i proizvodima od mesa. U ovom radu razvijena je metoda za određivanje benzo[a]pirena, benzo[a]antracena, benzo[b]fluorantena i hrizena tj. PAH4 jedinjenja u dimljenom mesu i proizvodima od mesa. Za ekstrakciju lipida i lipofilnih jedinjenja iz uzoraka korišćena je ubrzana ekstrakcija pomoću rastvarača. Ekstrakcija na čvrstoj fazi je korišćena kao postupak za uklanjanje molekula lipida iz ispitanih uzoraka. Identifikacija i kvantifikacija benzo[a]pirena, benzo[a]antracena, benzo[b]fluorantena i hrizena rađena je korišćenjem visokoefikasne tečne hromatografije sa fluorescentnim detektorom (HPLC-FL). Primenjeni su različiti uslovi HPLC analize (mobilna faza, HPLC kolona, temperatura peći, protok mobilne faze) u cilju postizanja optimalnih uslova za kvalitativnu i kvantitativnu analizu PAH4 jedinjenja.

Nutritional benefits of fish can be attributed primarily to the content of high-quality proteins, vitamins, elements and omega-3 polyunsaturated fatty acids. On the other hand, fish and fishery products are susceptible to contamination by chemicals that have been recognized as ubiquitous environmental pollutants such as toxic elements and polychlorinated organic compounds. Fish consumption could be therefore considered as one of the major sources of human exposure to all above-mentioned environmental contaminants. This paper is focused on mercury (Hg) that enters the environment by both, natural means (such as volcanic activity, erosions and weathering, factors which contribute to the presence of Hg in water, soil and the atmosphere) and human activities - mining, fossil fuels combustion, industrial emissions, direct application of fertilizers and fungicides as well as disposal of solid waste. Total concentrations of Hg were measured in fish muscle and canned fish products available on Serbian market. Total of 651 samples were analyzed: 350 samples of marine fish (hake, mackerel, sprat, scorpanea, gilthead, salmon), 34 samples of freshwater fish (trout and carp) and 267 samples of canned fish products (tuna and sardines). Data were collected during 2011. For the purpose of intake assessment, we used the data obtained from the GEMS/Food Consumption Cluster Diets database. According to this source, estimated average weekly consumption of marine fish is 106.4 g/week, while freshwater fish and canned fish contribute to the consumption with 29.4 g and 18.2 g/week respectively. Mercury concentrations in marine fish were in the range of 0.005-0.208 μgg-1 (mean 0.040 μgg-1); in freshwater fish 0.005- 0.099 μgg-1 (mean 0.020 μgg-1) and in canned products they were in the range of 0.005-0.642 μgg-1 (mean 0.064 μgg-1). All analyzed samples contained mercury below the maximum level laid down by the European Union and Serbian regulation. The estimated weekly intake for total mercury, based on mean mercury value in fish and average body mass of 70 kg, was 0.095 μg/kg b.w./week. Based on FAO/WHO recommended safe limit and on obtained results, we can conclude that the intake of mercury in the case of consuming fish and canned fish products is lower than the safe limit.

Nutritional benefits of fish can be attributed primarily to the content of high-quality proteins, vitamins, elements and omega-3 polyunsaturated fatty acids. On the other hand, fish and fishery products are susceptible to contamination by chemicals that have been recognized as ubiquitous environmental pollutants such as toxic elements and polychlorinated organic compounds. Fish consumption could be therefore considered as one of the major sources of human exposure to all above-mentioned environmental contaminants. This paper is focused on mercury (Hg) that enters the environment by both, natural means (such as volcanic activity, erosions and weathering, factors which contribute to the presence of Hg in water, soil and the atmosphere) and human activities - mining, fossil fuels combustion, industrial emissions, direct application of fertilizers and fungicides as well as disposal of solid waste. Total concentrations of Hg were measured in fish muscle and canned fish products available on Serbian market. Total of 651 samples were analyzed: 350 samples of marine fish (hake, mackerel, sprat, scorpanea, gilthead, salmon), 34 samples of freshwater fish (trout and carp) and 267 samples of canned fish products (tuna and sardines). Data were collected during 2011. For the purpose of intake assessment, we used the data obtained from the GEMS/Food Consumption Cluster Diets database. According to this source, estimated average weekly consumption of marine fish is 106.4 g/week, while freshwater fish and canned fish contribute to the consumption with 29.4 g and 18.2 g/week respectively. Mercury concentrations in marine fish were in the range of 0.005-0.208 μgg-1 (mean 0.040 μgg-1); in freshwater fish 0.005- 0.099 μgg-1 (mean 0.020 μgg-1) and in canned products they were in the range of 0.005-0.642 μgg-1 (mean 0.064 μgg-1). All analyzed samples contained mercury below the maximum level laid down by the European Union and Serbian regulation. The estimated weekly intake for total mercury, based on mean mercury value in fish and average body mass of 70 kg, was 0.095 μg/kg b.w./week. Based on FAO/WHO recommended safe limit and on obtained results, we can conclude that the intake of mercury in the case of consuming fish and canned fish products is lower than the safe limit. ; Nutritivna korist od konzumacije ribe ogleda se, pre svega u sadržaju visoko vrednih proteina, vitamina, makro i mikroelemenata i omega-3 polinezasićenih masnih kiselina. Sa druge strane, riba i proizvodi od ribe su u značajnoj meri podložni hemijskoj kontaminaciji ubikvitarnim zagađivačima kao što su teški metal i polihlorovana organska jedinjenja. Zbog svega ovoga, konzumacija ribe se smatra jednim od najznačajnijih izvora izloženosti navedenim kontaminentima. U radu je ispitivana kontaminacija živom koja se u spoljašnjoj sredini može naći kao posledica prirodnih procesa (vulkanska aktivnost, erozija tla i klimatska dešavanja koja doprinose prisustvu žive u vodi, zemljištu i atmosferi), kao i aktivnosti čoveka - eksploatacija ruda, sagorevanje fosilnih goriva, emisija industrijskih gasova, direktna primena veštačkih đubriva i fungicida, kao i neadekvatno odlaganje čvrstog otpada. Sadržaj ukupne žive je određivan u svežoj i konzervisanoj ribi sa srpskog tržišta. Ispitan je 651 uzorak: 350 uzoraka morske ribe (oslić, skuša, sardela, škarpina, orada i losos), 34 uzorka slatkovodne ribe (šaran i pastrmka) i 267 uzoraka konzervisane ribe (tuna i sardela). Svi uzorci su analizirani tokom 2011. godine. Za procenu unosa korišćeni su podaci iz 'GEMS/Food Consumption Cluster Diets database'. Prema ovom izvoru, procenjena prosečna nedeljna konzumacija morske ribe iznosi 106,4 g, slatkovodne 29,4 g dok je ova vrednost za konzervisane proizvode od ribe 18,2 g. Sardžaj žive u morskoj ribi se kretao u opsegu od 0,005 do 0,208 μgg-1 (srednja vrednost 0,040 μgg-1); u slatkovodnoj ribi 0,005-0,099 μgg-1 (srednja vrednost 0,020 μgg-1), dok se u konzervisanim ribljim proizvodima sadržaj žive kretao od 0,005 do 0,642 μgg-1 (srednja vrednost 0,064 μgg-1). Nivo žive u svim ispitanim uzorcima je bio ispod maksimalno dozvoljenih vrednosti propisanih relevantnom legislativom EU kao i domaćim propisima. Procenjeni nedeljni unos žive baziran na srednjoj vrednosti žive u konzumiranoj ribi i prosečnoj telesnoj težini od 70 kg, bio je 0,095 μg/kg telesne mase nedeljno. Na osnovu preporuka FAO/WHO i dobijenih rezultata, može se zaključiti da je unos žive pri konzumaciji morske i slatkovodne ribe i konzervisanih ribljih proizvoda, niži od preporučenih graničnih vrednosti.

Nutritional benefits of fish can be attributed primarily to the content of high-quality proteins, vitamins, elements and omega-3 polyunsaturated fatty acids. On the other hand, fish and fishery products are susceptible to contamination by chemicals that have been recognized as ubiquitous environmental pollutants such as toxic elements and polychlorinated organic compounds. Fish consumption could be therefore considered as one of the major sources of human exposure to all above-mentioned environmental contaminants. This paper is focused on mercury (Hg) that enters the environment by both, natural means (such as volcanic activity, erosions and weathering, factors which contribute to the presence of Hg in water, soil and the atmosphere) and human activities - mining, fossil fuels combustion, industrial emissions, direct application of fertilizers and fungicides as well as disposal of solid waste. Total concentrations of Hg were measured in fish muscle and canned fish products available on Serbian market. Total of 651 samples were analyzed: 350 samples of marine fish (hake, mackerel, sprat, scorpanea, gilthead, salmon), 34 samples of freshwater fish (trout and carp) and 267 samples of canned fish products (tuna and sardines). Data were collected during 2011. For the purpose of intake assessment, we used the data obtained from the GEMS/Food Consumption Cluster Diets database. According to this source, estimated average weekly consumption of marine fish is 106.4 g/week, while freshwater fish and canned fish contribute to the consumption with 29.4 g and 18.2 g/week respectively. Mercury concentrations in marine fish were in the range of 0.005-0.208 μgg-1 (mean 0.040 μgg-1); in freshwater fish 0.005- 0.099 μgg-1 (mean 0.020 μgg-1) and in canned products they were in the range of 0.005-0.642 μgg-1 (mean 0.064 μgg-1). All analyzed samples contained mercury below the maximum level laid down by the European Union and Serbian regulation. The estimated weekly intake for total mercury, based on mean mercury value in fish and average body mass of 70 kg, was 0.095 μg/kg b.w./week. Based on FAO/WHO recommended safe limit and on obtained results, we can conclude that the intake of mercury in the case of consuming fish and canned fish products is lower than the safe limit. ; Nutritivna korist od konzumacije ribe ogleda se, pre svega u sadržaju visoko vrednih proteina, vitamina, makro i mikroelemenata i omega-3 polinezasićenih masnih kiselina. Sa druge strane, riba i proizvodi od ribe su u značajnoj meri podložni hemijskoj kontaminaciji ubikvitarnim zagađivačima kao što su teški metal i polihlorovana organska jedinjenja. Zbog svega ovoga, konzumacija ribe se smatra jednim od najznačajnijih izvora izloženosti navedenim kontaminentima. U radu je ispitivana kontaminacija živom koja se u spoljašnjoj sredini može naći kao posledica prirodnih procesa (vulkanska aktivnost, erozija tla i klimatska dešavanja koja doprinose prisustvu žive u vodi, zemljištu i atmosferi), kao i aktivnosti čoveka - eksploatacija ruda, sagorevanje fosilnih goriva, emisija industrijskih gasova, direktna primena veštačkih đubriva i fungicida, kao i neadekvatno odlaganje čvrstog otpada. Sadržaj ukupne žive je određivan u svežoj i konzervisanoj ribi sa srpskog tržišta. Ispitan je 651 uzorak: 350 uzoraka morske ribe (oslić, skuša, sardela, škarpina, orada i losos), 34 uzorka slatkovodne ribe (šaran i pastrmka) i 267 uzoraka konzervisane ribe (tuna i sardela). Svi uzorci su analizirani tokom 2011. godine. Za procenu unosa korišćeni su podaci iz 'GEMS/Food Consumption Cluster Diets database'. Prema ovom izvoru, procenjena prosečna nedeljna konzumacija morske ribe iznosi 106,4 g, slatkovodne 29,4 g dok je ova vrednost za konzervisane proizvode od ribe 18,2 g. Sardžaj žive u morskoj ribi se kretao u opsegu od 0,005 do 0,208 μgg-1 (srednja vrednost 0,040 μgg-1); u slatkovodnoj ribi 0,005-0,099 μgg-1 (srednja vrednost 0,020 μgg-1), dok se u konzervisanim ribljim proizvodima sadržaj žive kretao od 0,005 do 0,642 μgg-1 (srednja vrednost 0,064 μgg-1). Nivo žive u svim ispitanim uzorcima je bio ispod maksimalno dozvoljenih vrednosti propisanih relevantnom legislativom EU kao i domaćim propisima. Procenjeni nedeljni unos žive baziran na srednjoj vrednosti žive u konzumiranoj ribi i prosečnoj telesnoj težini od 70 kg, bio je 0,095 μg/kg telesne mase nedeljno. Na osnovu preporuka FAO/WHO i dobijenih rezultata, može se zaključiti da je unos žive pri konzumaciji morske i slatkovodne ribe i konzervisanih ribljih proizvoda, niži od preporučenih graničnih vrednosti.

Background/Aim. Based on numerous studies in animals, the most prominent toxic effects of decabrominated di-phenyl ether (BDE-209) are observed in the liver, thyroid hormone homeostasis, reproductive and nervous systems. BDE-209 exhibits its toxic effects partly through the aryl hydrocarbon (Ah) receptor and consequent induction of hepatic microsomal enzymes. The aim of this study was to assess the hepatotoxic effect vs target tissue dose of BDE-209 in the subacutely orally exposed Wistar rats. Methods. Effects were examined on male Wistar rats, weighing 200-240 g, exposed to doses of 1,000, 2,000 or 4,000 mg BDE-209/kg body weight (bw)/day by gavage during 28 days. Animals were treated according to the decision of the Ethics Committee of the Military Medical Academy, No 9667-1/2011. Evaluation of the hepatotoxic effect was based on: relative liver weight water and food intake, biochemical parameters of liver function [aspartate amino transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gama glutamyl transferase (γ-GT)], and oxidative stress parameters in liver homogenates [malondialdehiyde (MDA), superoxide dismutase (SOD), -SH] and morphological and pathohistological changes in the liver. For the assessment of internal dose - response relationship, lower confidence limit of Benchmark dose (BMDL) of 5% or 10% i.e. BMDL5 or BMDL10, were calculated using PROAST software. Results. After the application of 1,000, 2,000 or 4,000 mg BDE-209/kg bw/day, the concentrations of BDE-209 measured in liver were 0.269, 0.569 and 0.859 mg/kg of liver wet weight, (ww) respectively. Internal doses correlated with external (r = 0.972; p < 0.05) according to equation: internal dose (mg BDE-209/kg of liver ww) = 0.0002 ' external dose (mg/kg bw/day) + 0.0622. Hepato-toxicity was demonstrated based on significant increase in AST and γ-GT activities and the degree of histopathological changes. The lowest BMDL5 of 0.07228 mg BDE-209/kg of liver ww, correlating to external dose of 39 mg/kg/day, indicated the increase of AST activity as the most sensitive biomarker of BDE-209 hepatotoxicity in subacutely ex-posed rats. Conclusion. The results of the present work add up to the issue of BDE-209 toxicity profile with a focus on relationship between internal dose and hepatotoxicity. Critical internal dose for the effect on AST of 0.07 mg/kg of liver ww, corresponding to external dose of 39 mg/kg/day, is the lowest dose ever observed among the studies on BDE-209 hepatotoxicity. For the persistent sub-stances with low absorption rate such as BDE-209, critical effect based on internal dose in majority of cases is considered as more precisely defined than the effect established based on external dose, particularly.

Background/Aim. Based on numerous studies in animals, the most prominent toxic effects of decabrominated di-phenyl ether (BDE-209) are observed in the liver, thyroid hormone homeostasis, reproductive and nervous systems. BDE-209 exhibits its toxic effects partly through the aryl hydrocarbon (Ah) receptor and consequent induction of hepatic microsomal enzymes. The aim of this study was to assess the hepatotoxic effect vs target tissue dose of BDE-209 in the subacutely orally exposed Wistar rats. Methods. Effects were examined on male Wistar rats, weighing 200-240 g, exposed to doses of 1,000, 2,000 or 4,000 mg BDE-209/kg body weight (bw)/day by gavage during 28 days. Animals were treated according to the decision of the Ethics Committee of the Military Medical Academy, No 9667-1/2011. Evaluation of the hepatotoxic effect was based on: relative liver weight water and food intake, biochemical parameters of liver function [aspartate amino transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gama glutamyl transferase (γ-GT)], and oxidative stress parameters in liver homogenates [malondialdehiyde (MDA), superoxide dismutase (SOD), -SH] and morphological and pathohistological changes in the liver. For the assessment of internal dose - response relationship, lower confidence limit of Benchmark dose (BMDL) of 5% or 10% i.e. BMDL5 or BMDL10, were calculated using PROAST software. Results. After the application of 1,000, 2,000 or 4,000 mg BDE-209/kg bw/day, the concentrations of BDE-209 measured in liver were 0.269, 0.569 and 0.859 mg/kg of liver wet weight, (ww) respectively. Internal doses correlated with external (r = 0.972; p lt 0.05) according to equation: internal dose (mg BDE-209/kg of liver ww) = 0.0002 ' external dose (mg/kg bw/day) + 0.0622. Hepato-toxicity was demonstrated based on significant increase in AST and γ-GT activities and the degree of histopathological changes. The lowest BMDL5 of 0.07228 mg BDE-209/kg of liver ww, correlating to external dose of 39 mg/kg/day, indicated the increase of AST activity as the most sensitive biomarker of BDE-209 hepatotoxicity in subacutely ex-posed rats. Conclusion. The results of the present work add up to the issue of BDE-209 toxicity profile with a focus on relationship between internal dose and hepatotoxicity. Critical internal dose for the effect on AST of 0.07 mg/kg of liver ww, corresponding to external dose of 39 mg/kg/day, is the lowest dose ever observed among the studies on BDE-209 hepatotoxicity. For the persistent sub-stances with low absorption rate such as BDE-209, critical effect based on internal dose in majority of cases is considered as more precisely defined than the effect established based on external dose, particularly. ; Uvod/Cilj. Prema podacima iz brojnih studija na životinjama, dekabromovani difeniletar (BDE-209) najznačajnije toksične efekte ispoljava na jetri, homeostazi hormona štitaste žlezde, reproduktivnom i nervnom sistemu. BDE-209 ispoljava toksične efekte delom preko receptora za aromatične ugljovodonike (Ah) i posledične indukcije mikrozomalnih enzima jetre. Cilj rada bio je procena hepatotoksičnog efekta u odnosu na dozu BDE-209 u ciljnom tkivu kod subakutno oralno eksponovanih Wistar pacova. Metode. Efekti su ispitivani na mužjacima Wistar pacova, mase 200-240 g, koji su putem oralne sonde primali doze od 1 000, 2 000 ili 4 000 mg BDE-209/kg telesne mase (tm) dan, tokom 28 dana. Životinje su tretirane u skladu sa odlukom Etičkog komiteta Vojnomedicinske akademije u Beogradu br. 9667-1/2011. Procena hepatotoksičnih efekata bazirana je na merenju relativne mase jetre, unosa vode i hrane, biohemijskih parametara funkcije jetre [aspartat aminotransferaza (AST), alanin amino-transferaza (ALT), alkalna fosfataza (ALP), gama glutamil transferaza (γ-GT)], parametara oksidativnog stresa u homogenatima jetre [malondialdehid (MDA), superoksid dizmutaza (SOD), -SH)] i morfoloških i histoloških promena na jetri. Za procenu odnosa interna doza - odgovor izračunavana je donja granica pouzdanosti granične Benchmark doze (BMDL) od 5% (BMDL5) ili 10% (BMDL10) primenom PROAST softvera. Rezultati. Koncentracije BDE-209 iznosile su 0,269, 0,569 i 0,859 mg/kg jetre nakon aplikacije 1 000, 2 000, odnosno 4 000 mg BDE-209/kg tm/dan. Interna doza u našoj studiji korelisala je sa eksternom dozom prema jednačini: interna doza (mg BDE-209/kg jetre) = 0,0002 ' eksterna doza (mg/kg tm/dan) + 0,0622 (r = 0,972; p lt 0,05). Hepatotoksičnost je potvrđena na osnovu nalaza o povećanju aktivnosti enzima AST i γ-GT, kao i stepena patohistološkog oštećenja jetre. Najniža BMDL5 u eksperimentu od 0,07228 mg BDE-209/kg jetre, koja koreliše sa eksternom dozom od 39 mg/kg tm/dan izračunata je za aktivnost AST i ukazuje na to da je aktivnost AST ujedno i najosetljiviji biomarker hepatotoksičnosti BDE-209 kod subakutno eksponovanih pacova. Zaključak. Rezultati prezentovane studije daju doprinos pitanju toksikološkog profila BDE-209 sa fokusom na odnos između interne doze i hepatotoksičnih efekata. Kritična interna doza za efekat na AST od 0,07 mg/kg jetre, koja koreliše sa eksternom dozom od 39 mg/kg tm/dan, jeste ujedno i najniža kritična doza do sada definisana za hepatotoksične efekte BDE-209. Kritičan efekat koji se bazira na dozi u ciljnom tkivu u većini slučajeva može se smatrati preciznije definisanim od kritičnog efekta definisanog na bazi oralno primenjene doze, naročito za nedegradabilne supstance sa niskim stepenom apsorpcije, kao što je BDE-209.