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.
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. 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 should be evaluated and established concerning national legislative frame. ; 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 se nacionalnim zakonodavstvom odrede i ustanove maksimalno dozvoljene koncentracije sadržaja ovog metala u biljnim lekovitim sirovinama.
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.