1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

1st INTERNATIONAL CONGRESS AND WORKSHOP OF FORENSIC TOXICOLOGY

ABSTRACT BOOK

Ankara-TÜRKĠYE November 29-30, 2014

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

TABLE of CONTENTS

Information Welcome 3 Sponsors 4 Host 7 Contributors 7 Orginising Committee 7 Scientific Secretary 8 Scientific Committee 8 Abstracts Oral Presentations 17 Poster Presentations 57

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

WELCOME Dear Participants, On behalf of the Society of Forensic Toxicology, Ankara University Institute of Forensic Sciences and Society of Forensic Scientists, it is our great pleasure to invite all of you to the 1st International Congress and Workshop of Forensic Toxicology. This Congress is aimed to bring together forensic toxicologists from different countries and to share and enhance knowledge on latest international researches on the subject. However, topics will not be limited only to forensic issues, and will cover genetic toxicology, occupational diseases and toxicology, post-mortem toxicology, ethical and legal requirements in clinical research, heavy metals and toxicology, and daily life and toxicology. There will be various interactive poster sessions and a trade exhibition. The program features the latest developments in forensic sciences and in other toxicology related areas. The Congress venue is in the capital Ankara with various accommodation opportunities, restaurants, museums, pubs and cafes. Beside its historic buildings, the city has many peerless museums such as Museum of Anatolian Civilizations and Ethnographic Museum,Augustus Temple and Roman Baths, and other landmarks including Mausoleum of Atatürk, Hacı Bayram Mosque and Ankara Castle. We do of course hope that will also avail yourselves of the beautiful meeting venue and all that it has to offer and take this opportunity to interact with other colleagues and students. We are looking forward you to join us in Ankara in November 2014. Let’s meet in 1st ForeTox!

Presidents of the 1st International Workshop and Congress of Forensic Toxicology

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

SPONSORS MAIN SPONSOR

SPONSORS

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

HOST

Ankara University Society of Forensic Toxicology Ankara University, Institute of Forensic Sciences Society of Forensic Scientists

CONTRIBUTORS Turkish Society of Toxicology The Council of Forensic Medicine

ORGANISING COMMITTEE Asım HOCAOĞLU, Turkish Medicine and Medical Device Agency, TÜRKİYE Ayten NAMLI, Ankara University, Faculty of Agriculture, TÜRKİYE Bilge Ahsen KARA,The Ministry of Health, Turkish Public Health Association, TÜRKİYE Ceylan BAL, The Ministry of Health, Ankara Occupational Diseases Hospital, TÜRKİYE Dilek AKYÜZLÜ, Ankara University, Institute of Forensic Sciences, TÜRKİYE Emrah DURAL, Ankara University, Institute of Forensic Sciences, TÜRKİYE Esma SÖYLEMEZ, Middle Black Sea Transitional Zone Agricultural Research Station Directorate, TÜRKİYE Esra BALCIOĞLU, Ankara University, Institute of Forensic Sciences, TÜRKİYE Fezile ÖZDEMĠR, TURKISH REPUBLIC OF NORTHERN CYPRUS Kenan Can TOK, Ankara University, Institute of Forensic Sciences, TÜRKİYE Neslihan ALPAY ARAL, The Ministry of Justice, The Council of Forensic Medicine, TÜRKİYE Murat MERT, The Ministry of Justice, The Council of Forensic Medicine, TÜRKİYE Mustafa Tuğrul GÖKTAġ, Department of Medical Pharmacology, Faculty of Medicine, Yıldırım Beyazıt University, TÜRKİYE Sultan PEHLĠVAN, The Ministry of Justice, The Council of Forensic Medicine, TÜRKİYE

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

SCIENTIFIC SECRETARY

Asım HOCAOĞLU, Turkish Medicine and Medical Device Agency, TÜRKİYE Ceylan BAL, The Ministry of Health, Ankara Occupational Diseases Hospital, TÜRKİYE Dilek AKYÜZLÜ, Ankara University, Institute of Forensic Sciences, TÜRKİYE

SCIENTIFIC COMMITTEE

Adalat HASANOV, The Department of Pathological Anatomy and Forensic Medical Examination, Azerbaijan Medical University, AZERBAIJAN

Ahmet AYDIN, Department of Pharmacy, Yeditepe University, TÜRKİYE

Ahmet DOĞRUL, Department of Medical Pharmacology, Gulhane Military Medical Academy, TÜRKİYE

Ahmet SAYAL, Pharmaceutical Sciences Center, Gulhane Military Medical Academy, TÜRKİYE

Ali KOÇAK, Science Department, John Jay College of Criminal Justice, New York, USA

Ali PEHLĠVAN, Ankara Training and Research Hospital, TÜRKİYE Altay SUROY, Kosova Constitutional Court, Kosovo

Aristidis Michael TSATSAKIS, Department of Forensic Sciences & Toxicology, Faculty of Medicine, University of Crete, Heraklion, GREECE

Arsim GERXHALIU, Kosovo Institute of Forensic Medicine, KOSOVO

Asım HOCAOĞLU, Turkish Medicine and Medical Device Agency, TÜRKİYE

Aslıhan AVCI, Department of Medical Biochemistry, Faculty of Medicine, Ankara University, TÜRKİYE

Asude GÖKMEN, The Ministry of Justice, The Council of Forensic Medicine, TÜRKİYE

Asuman ÖZGÖZ, Department of Nutrition and Dietetics, Fazıl Boyner School of Health, Kastamonu University, TÜRKİYE

Asuman SUNGUROĞLU, Department of Medical Biology, Faculty of Medicine, Ankara University, TÜRKİYE

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

Ayla Sevim EROL, Department of Anthropology, Faculty of Language, History and Geography, Ankara University, TÜRKİYE

Aysel Çağlan KARASU BENLĠ, Gazi University, Institute of Science, TÜRKİYE

AyĢegül YÜKSELTÜRK, Department of Nutrition and Dietetics, Fazıl Boyner School of Health, Kastamonu University, TÜRKİYE

Ayten NAMLI, Department of Soil Science and Plant Nutrition, Faculty of Agriculture, Ankara University, TÜRKİYE

Baha Berk ARPAK, The Ministry of Justice, The Council of Forensic Medicine, TÜRKİYE

Baki KOYUNCU, Ankara University, Faculty of Engineering, Department of Computer Engineering, TÜRKİYE

Bayram YÜKSEL, Ankara Police Forensic Laboratories, Turkish National Police, TÜRKİYE

Belma KOÇER-GÜMÜġEL, Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Hacettepe University, TÜRKİYE

Bilge Ahsen KARA, The Ministry of Health, Turkish Public Health Association, TÜRKİYE

Blerim OLLURI, Kosovo Institute of Forensic Sciences, Kosovo

Bora ÖZDEMĠR, Department of Forensic Medicine, Faculty of Medicine, Inonu University, TÜRKİYE

Buket ALPERTUNGA, Department of Pharmaceutical Toxicology, Faculty of Pharmacy, İstanbul University, TÜRKİYE

Bulut DEMĠREL, Emergency Medicine, Ankara Training and Research Hospital, TÜRKİYE

Caner YENĠDÜNYA, Department of Criminal and Criminal Procedural Law, Faculty of Law, Marmara University, TÜRKİYE

Cem Mehmet ÇETĠN, Turkish National Police, TÜRKİYE

Cemal AKAY, Center for Pharmaceutical Sciences, Gulhane Military Medical Academy, TÜRKİYE

Ceylan BAL, Ankara Occupational Diseases Hospital, TÜRKİYE

Chang-En PU, Deputy Director General at MJIB, TAIWAN

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

Deniz TEKĠN, Department of Children Health and Diseases, Faculty of Medicine, Ankara University, TÜRKİYE

Dilek KAYA-AKYÜZLÜ, Department of Forensic Chemistry and Forensic Toxicology, Institute of Forensic Science, Ankara University, TÜRKİYE

Dilek ÖZCENGĠZ, Department of Anesthesiology, Faculty of Medicine, Cukurova University, TÜRKİYE

Ebru GÜRLEYĠK, The Ministry of Justice, The Council of Forensic Medicine, TÜRKİYE

Ekrem MUġ, Turkish National Police Academy, TÜRKİYE

Emanuela TESTAI, Senior/Executive Scientist at Istituto Superiore di Sanità (National Institute for Health, Rome, Italy

Emrah DURAL, Depertman of Forensic Chemistry and Forensic Toxicology, Institute of Forensic Science, Ankara University, TÜRKİYE

Engin TUTKUN, Ankara Occupational Diseases Hospital, TÜRKİYE

Ersin KARAPAZARLIOĞLU, Turkish National Police Academy, TÜRKİYE

Ertan SEVEN, Turkish National Police Forensic Laboratory, TÜRKİYE

Esra BALCIOĞLU, Department of Forensic Chemistry and Forensic Toxicology, Institute of Forensic Science, Ankara University, TÜRKİYE / Faculty of Health and Sciences, De Montfort University, UK

Esra GÜNDÜZ, Turgut Özal University, Faculty of Medicine, Department of Medical Genetics, TÜRKİYE

EĢref KÜÇÜK, Faculty of Law, TOBB University of Economics & Technology, TÜRKİYE

Eun- Kee PARK, Department of Medical Humanities and Social Medicine, College of Medicine, Kusan University, Busan, KOREA

Fatih KOLAY, Turkish National Police, TÜRKİYE

Fatih YAĞMUR, Department of Medical Sciences, Faculty of Medicine, Istanbul medeniyet University, TÜRKİYE

Fatma Meriç YILMAZ, Department of Biochemistry, Faculty of Medicine, Yıldırım Beyazıt University, TÜRKİYE

Feride SEVERCAN, Department of Biological Sciences, Middle East Technical University, TÜRKİYE

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

Fezile ÖZDEMĠR, TURKISH REPUBLIC OF NORTHERN CYPRUS

Figen ÜNLÜ ERKOÇ, Gazi University, Faculty of Education, TÜRKİYE

Göknur AKTAY, Department of Pharmaceutical Sciences, Inonu University, TÜRKİYE

Gülden OMURTAG, Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Marmara University, İstanbul, TÜRKİYE

Gürol CANTÜRK, Department of Medical Sciences, Faculty of Medicine, Ankara University, TÜRKİYE

Habibul AHSAN, Department of Health Studies; The University of Chicago, USA

Hamdi AKAN, Ankara University, Faculty of Medicine, Ankara, TÜRKİYE

Hande GÜRER ORHAN, Department of Pharmaceutical Toxicology, Ege University, TÜRKİYE

Hanım HALĠLOVA, Azebaijan Women Laws Society, AZERBAIJAN

Hanife ALKURT ALKAN, The Ministry of Justice, The Council of Forensic Medicine, TÜRKİYE

Heidi FOTH, Institute of Environmental Toxicology, Martin Luther University, Halle, GERMANY

Hınç YILMAZ, Ankara Occupational Diseases Hospital, TÜRKİYE

Hilal ĠLBARS, Turkish Medicine and Medical Device Agency, TÜRKİYE

Hilmi ORHAN, Department of Pharmaceutical Toxicology, Ege University, TÜRKİYE

Hülya YÜKSELOĞLU, Institute of Forensic Medicine, Istanbul University, TÜRKİYE

Hüseyin BEKĠR, University of Ioannina, GREECE

Ġrfan KORKUSUZ, The Ministry of Justice, The Council of Forensic Medicine, TÜRKİYE

Ġsmail ÇAKIR, Institute of Forensic Medicine, Istanbul University, TÜRKİYE

Ġ. Hamit HANCI, Institute of Forensic Science, Ankara University, TÜRKİYE

Jamal MUSAYEV, The Department of Pathological Anatomy and Forensic Meidcal Examination, Azerbaijan Medical University, AZERBAIJAN

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

Kenan Can TOK, Depertman of Forensic Chemistry and Forensic Toxicology, Institute of Forensic Science Ankara University, TÜRKİYE

Lale KARABIYIK, Department of Anesthesiology, Faculty of Medicine, Gazi University, TÜRKİYE

Levent KENAR, Chemical, Biological, Radiological and Nuclear Medical Science Department of Defense, Gulhane Military Medical Academy, TÜRKİYE

Mahmut SELVĠ, Gazi University, Faculty of Education, TÜRKİYE

Mehmet CAVLAK, The Ministry of Justice, The Council of Forensic Medicine, TÜRKİYE

Mehmet ERYILMAZ, Department of Emergency Medicine, Gulhane Military Medical Academy, TÜRKİYE

Mehtap ÖZDEMĠR YÖNDEM, The Ministry of Justice, The Council of Forensic Medicine, TÜRKİYE

Miyase ODABAġI YAYLAGÜL, Vocational School of Health Services, Adıyaman University, TÜRKİYE

Muazzez Çelik KARAKAYA, Department of Geological Engineering, Faculty of Engineering, Selçuk University, TÜRKİYE

Muharrem ÖZEN, Department of Criminal and Criminal Procedural Law, Faculty of Law, Ankara University, TÜRKİYE

Mukaddes GÜRLER, Department of Medical Biochemistry, Faculty of Medicine, Hacettepe University, TÜRKİYE

Murat MERT, The Ministry of Justice, The Council of Forensic Medicine, TÜRKİYE

Mustafa KARAPĠRLĠ, The Ministry of Justice, The Council of Forensic Medicine, TÜRKİYE

Mustafa Tuğrul GÖKTAġ, Department of Medical Pharmacology, Faculty of Medicine, Yıldırım Beyazıt University, TÜRKİYE

Münevver AÇIKKOL, Institute of Forensic Sciences, Istanbul University, TÜRKİYE

Neslihan GÜRBÜZ, Laboratory Animals Raising and Experimental Researches Center, Faculty of Medicine, Gazi University, TÜRKİYE

Neslihan ALPAY ARAL, Institute of Forensic Medicine, TÜRKİYE

Nesrin ÇOBANOĞLU, Department of Medical Ethics and History of Medicine, Faculty of Medicine, Gazi University, TÜRKİYE

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

Nevzat ARTIK, Department of Food Engineering, Faculty of Engineering, Ankara University, TÜRKİYE

Nilgün ġEN, Institute of Forensic Sciences, Turkish National Police Academy, TÜRKİYE

NurĢen BAġARAN, Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Hacettepe University, TÜRKİYE

Onur ERDEM, Pharmaceutical Sciences Center, Gulhane Military Medical Academy, TÜRKİYE

Orhan ATAKOL, Department of Chemistry, Faculty of Arts&Sciences, Ankara University, TÜRKİYE

Osman CELBĠġ, Department of Forensic Medicine, Faculty of Medicine, Inonu University, TÜRKİYE

Parvez HARĠS, School of Allied Health Sciences, Faculty of Health and Life Sciences, De Montfort University, UK

Pelin KILIÇ, Turkish Medicine and Medical Device Agency, Republic of Turkey Ministry of Health, TÜRKİYE

Pervin GÜRLER, TRNC Police Headquarters, TRNC Rabia SARIKAYA, Gazi University, Faculty of Education, TÜRKİYE Recep AKDUR, Department of Population Health, Faculty of Medicine, Ankara University, TÜRKİYE

Recep BENLĠ, Constitutional Court of the Republic of Turkey, TÜRKİYE

Salih CENGĠZ, Institute of Forensic Medicine, Cerrahpaşa Faculty of Medicine, Istanbul University, TÜRKİYE

Selda MERCAN, Institute of Forensic Sciences, Istanbul University, TÜRKİYE

Sema TETĠKER, Department of Geological Engineering, Faculty of Engineering and Architecture, Batman University, TÜRKİYE

Semra BENZER, Gazi University, Faculty of Education, TÜRKİYE

Semra ġARDAġ, Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Marmara University, TÜRKİYE

San Chang CHYUEH, Chief of Toxicology, Bureau of Investigation, Ministry of Justice, TAIWAN, Republic Of China

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

Serap YALÇIN, Department of Food Engineering, Ahi Evran University, TÜRKİYE

Seung HOON LEE, Korea Environment Corporation, Ministry of Environment, KOREA

Sinan SÜZEN, Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Ankara University, TÜRKİYE

Sreeparna BANERJEE, Department of Biological Sciences, Middle East Technical University, TÜRKİYE

Sultan PEHLĠVAN, Department of Forensic Pathology, Institute of Forensic Medicine, TÜRKİYE

Tahir NALBANTÇILAR, Department of Geological Engineering, Faculty of Engineering and Architecture, Batman University, TÜRKİYE

Talat CANBOLAT, Department of Labour and Social Security Law, Faculty of Law, Marmara University, TÜRKİYE

Taner BORA, Turkish National Police, Ankara Police Forensic Laboratory, TÜRKİYE

Ulvi Reha FĠDANCI, Departments of Biochemistry & Basic Sciences of Veterinarian, Faculty of Veterinary, Ankara University, TÜRKİYE

Üner ÜLKÜER, Institute of Forensic Sciences, Ankara University, TÜRKİYE

Yalçın BÜYÜK, The Ministry of Justice, The Council of Forensic Medicine, TÜRKİYE

Yalçın DUYDU, Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Ankara University, TÜRKİYE

Yalçın ÖZKAN, Pharmaceutical Sciences Center, Gulhane Military Medical Academy, TÜRKİYE

Yıldırım BEYATLI DOĞAN, Department of Mental Health and Diseases, Faculty of Medicine, Ankara University, TÜRKİYE

Yu CHEN, Departments of Population Health (Epidemiology) and Environmental Medicine, New York University, USA

Yücel DENER, Turkish Medicine and Medical Device Agency, Republic of Turkey Ministry of Health, TÜRKİYE

Yüksel ÖRGÜN, Department of Geological Engineering, Faculty of Mining, Istanbul Technical University, TÜRKİYE

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

Zekeriya ALANOĞLU, Department of Surgical Sciences, Faculty of Medicine, Ankara University, TÜRKİYE

Zeliha KAYAALTI, Department of Forensic Toxicology, Institute of Forensic Sciences, Ankara University, TÜRKİYE

Zerrin ERKOL, Department of Forensic Medicine, Faculty of Medicine, Abant İzzet Baysal University, İstanbul, TÜRKİYE

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

ABSTRACTS

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

ORAL PRESENTATIONS

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

S1. TOXICOGENOMICS OF HEALTH EFFECTS OF EXPOSURE

Habibul AHSAN The University of Chicago, Chicago, IL, USA

Arsenic exposure to human is a major public health issue in many countries, increasing risk for a wide array of diseases, including cancer, cardiovascular and respiratory diseases. However, the molecular and genomic basis of arsenic in human is not well understood. Through a genome-wide association study of nearly 3,000 Bangladesh individuals we identified the AS3MT gene (arsenite methyltransferase; 10q24.32) variants to be associated with arsenic-related metabolism and toxicity phenotypes, confirming the basis for genetically-determined susceptible subgroups for arsenic toxicity in humans. Among a sample of 1,800 participants with genome-wide SNP and gene expression data, we evaluated differential gene expressions in relation to arsenic exposure. These analyses identified a large number of arsenic-associated genes from various biological pathways, revealing a number of molecular targets of arsenic exposure in humans. Finally, we evaluated the association between blood and urinary total arsenic concentrations, and epigenome-wide white blood cell DNA methylation in a subset of 400 individuals.We identified fourgenome-wide significant differentially methylated CpG sites (PLA2G2C, SQSTM1,SLC4A4 and IGH genes) to be associated with urinary and blood total arsenic concentration, suggesting that epigenetic modifications may be an important pathway underlying arsenic toxicity. In conclusion, our integrated toxicogenomic analyses of arsenic exposure identified specific genetic susceptibility variants as well as arsenic-associated differentially methylated and expressed loci which may inform mechanisms underlying arsenic toxicity as well as potential pathways for future interventions. Details of these genomic determinants and molecular alterations related to arsenic toxicity will be presented at the conference.

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S2. PHARMACOGENETICS APPLICATIONS IN FORENSIC TOXICOLOGY

H. Sinan SÜZEN Ankara University, Faculty of Pharmacy, Department of Toxicology, Tandogan-Ankara, TÜRKĠYE

Pharmacogenetics is genetic basis of medication response and adverse drug reactions (ADRs) in pharmacotherapy. Over the last three decades, the role of genetic variation in drug response and toxicity has been increasingly recognised (Scott, 2011). Factors affecting an individual‘s pathophysiological phenotype related to drug efficacy and ADRs are genetic variations, (gene deletions, gene duplications, sequence variation), developmental stage (age, gender), physiological factors (mental and physical stress, hormonal changes, seasonal and circadian factors), environmental factors (personal environmental history, lifestyle, diet, exposure to environmental toxins, concomitant use of alcohol(s) and drugs), potential, specific associations (diabetes, obesity, gut microbiology). Among these factors, genetic variations has an important role in pharmacotherapy since inter-individual variations in DNA sequence related to drug pharmacokinetics or pharmacodynamics, including polymorphisms in genes encoding transporters, drug-metabolizing , receptors and other proteins.

Pharmaceutical agents are one of the most commonly determined matters of adverse events, causing in important morbidity and mortality worldwide. Among deaths attributed to medications, the most common drug categories are opioid analgesics, psychotherapeutics, and antiepileptic and antiparkinsonism drugs (Jones, 2013). Despite well-defined reference drug toxicity levels are established, interpretive hindrances are usually encountered the field of forensic toxicology in some cases. Pharmacogenetics has the potential to become a supplemental tool for the forensic toxicology in the interpretation of drug-related deaths, especially accidental drug poisoning or cases of sudden death with normal autopsy (Sajantila et al., 2010).

Several different types of changes exist in the DNA sequence which range from single nucleotide polymorphisms (SNPs), indel/s to larger structural alterations such as copy number variations (CNVs) and big deletions (Shen et al., 2013). These genetic variations in the genes which encode the drug-metabolizing enzymes may lead to normal (extensive metabolisers,

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

EMs), deficient/low (poor metabolisers-PMs/intermediate metabolisers-IMs), or higher activities (ultrarapid metabolisers, UMs). Individuals having variant alleles are at increased risk of encountering from adverse drug reactions as a result of drug overdose or of experiencing therapeutic failure by reason of poor metabolism of a prodrug to the active metabolite. In contrast, UMs have significantly elevated enzyme activity, which can result in subtherapeutic serum concentrations of the medicine.

Interpretation of toxicology results from the perspective of pharmacogenetics has a great potential in decisions concerning the cause and manner of death, as well as in legal proceedings. In the forensic context, pharmacogenetics may serve as an adjunct for certifying drug-related fatalities.

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S3. THE IMPORTANCE OF BIOMONITORING OF DNA DAMAGE IN OCCUPATIONAL EXPOSURE TO CHEMICALS

A. NurĢen BAġARAN Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Toxicology, 06100, Ankara, TÜRKĠYE

People in various occupational settings have the potential to be exposed to some hazardous chemicals which are used in industry and in agriculture. Since many of these chemicals are known to be genotoxic and can lead to genetic alteration, the exposures of these substances have been associated with an increased risk for certain diseases including cancer. Occupational exposure has been estimated to account for nearly 10% of all human cancer. The level of the exposure depends on the working area, duration of exposure and individual protective measures. The measurement of molecular or cellular biomarkers as the indicators of exposure or preventive factors has many applications in occupational toxicology. Reliable and fast methods are necessary for screening workers professionally at risk in different occupational settings. The evaluation of DNA damage and DNA repair as the biomarker of genotoxic substance exposure and cancer risk is important in biomonitoring and molecular epidemiological studies. The Comet assay which has been regarded as simple, inexpensive, reliable, rapid and trusted biomarker assay, determines DNA damage and DNA repair in single cells. In this presentation, the importance of biomonitoring of DNA damage that can be assessed by Comet assay in some occupations will be presented. Work characteristics affecting the DNA damage of the exposed workers and the existence of policies governing chemical exposures will also be discussed.

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W1.ANALYTICAL ASPECTS FOR LONG-TERM AND ACUTE INTOXICATION IN OCCUPATIONAL CLINICAL AND POSTMORTEM TOXICOLOGY AND OF BIO MONITORING STUDIES FOR LINKING TO DISEASES

Aristidis Michael TSATSAKIS Professor and Director, MSc, PhD, DSc, ERT Department of Toxicology & Forensic Science, Medical School, University of Crete, Voutes Campus, Heraklion 71003, GREECE

Linking of chemical intake or exposure to health effects to diseases and to death has been extensively reported in experimental studies and in epidemiology research. Bio-monitoring of human exposure to hazards nowadays plays crucial role in the formation of governmental public health policy that consists in the acceptance of required decisions, development of a laws, regulations, administrative actions and practice aimed to achieve specific health care goals within a society. And these decisions, regulations and laws can have important impact on the community organization, on the personal behavior and habits and even on directions of technological progress. It is obvious that bio monitoring data used for the acceptance of the mentioned measures should be reliable and thoroughly validated. Recent developments in chromatography-mass spectrometry ensure the requested validity and extend substantially the potential of bio monitoring by enhancing speed and efficiency of chromatographic and mass analysis. Also these achievements contribute in the development of new approaches in bio- monitoring and in particular screening for non-target and unknown compounds. Nevertheless one major problem for the inadequacy of validated linking of chemical exposure to health problems refers to the biomarkers used for the studies. This issue is complicated due to the complexity of the overall human exposure and the multiple effects excreted by one chemical in terms of the mechanisms of toxicity. There are considerable uncertainties concerning health risks as a consequence of long term and low dose chemical exposure. An important factor in these apparent discrepancies is the difficulty in reliable identification of exposed and control groups. Furthermore, the characteristics of exposure, in particular concerning duration and involvement of variable environmental factors and mixtures make any epidemiological approach very difficult. Real life is a variability and diversity of exposures the overall effect of which is pending on the certain case. The complex issue of linking exposures to diseases/health effects can be summarized under the term ―web of interactions‖. Using database-derived terminology, the type of problems and interactions can be described as a

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many-to-many relationship. There is a long list of issues that can lead to controversies (e.g. hidden effects from other pollutants, unknown or not studied confounders, issues of chemical analysis, misclassification of exposure or disease, variability in response etc.). Exposure issue effects in reality are not monomodal/monotonic events even in very low, low and/or high exposures. Principles and applications of hair analysis and a brief overview of published studies concerning hair analysis of various chemical groups in bio monitoring of pollutants low level long-term exposure acute will be presented. Furthermore, the role of in-vivo experiments in method optimization and validation will be discussed. Findings from the recent studies on polybrominated ethers, pyrethroids, neonicotinoids and arsenic will be reported. Cross-sectional studies on pregnant women and the neonates with documented prenatal pesticide low level chronic exposure revealed the impact of pesticides on fetus development and pregnancy outcomes and also for hypospadias in children. Hair analysis is a subject of great interest because it provides information on chronic and acute exposure with many applications in several areas of medical, forensic and environmental science. Hair is a suitable matrix for the assessment of exposure to chemicals (e.g. drugs, pharmaceuticals, environmental pollutants, pesticides) as hair possesses certain advantages (time-efficient, practical, cost effective, and non-invasive) over the conventional biological samples (blood, urine, saliva). Moreover hair traps information for prolonged periods of time while a dose- response relationship between the drug dose and their detected levels in the hair has been established in many studies. Hair testing has already been applied in various forensic investigations (autopsy, criminal) in doping control and in clinical practice to check compliance to therapy regime for people under long-term treatment. The knowledge of the drugs deposition variability in different anatomical hair sites is of significant importance to obtain and evaluate the data.

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S4. OCCUPATIONAL EXPOSURE TO ASBESTOS: WHAT WE ARE MISSING FROM A PREVIOUS EXPOSURE TO ASBESTOS

Eun-Kee PARK Department of Medical Humanities and Social Medicine, College of Medicine, Kosin University, Busan, Republic of KOREA

Exposure toasbestos at occupational settings is by far the leading risk factor for work-related diseases in the World.Despite all forms of asbestos are known as a human carcinogen, it is still circulated in global market andis banned at only 55 countries. The use of asbestos is closely related to the development of asbestos-related diseases (ARDs) including mesothelioma and lung cancer. It is reported that a ratio of mesothelioma and asbestos- induced lung cancer is 1:1. However, lung cancer patients are seldom interviewed to ascertain additional risk factors such as asbestos.

Age-adjusted mortality rate of mesothelioma was 4.9 per million population and increased by 5.4% per year over 1994-2008 that was consequently more than doubled during this period.

Global estimation of potential years of life lost (PYLL) due to mesotheliomafrom 1994 to 2010 indicated a total of 2.18 million years (PYLL) or an annual average PYLL of 201,000 years. The average PYLL per decedent was 17 years.

In Asian countries, asbestos use is continuing due to economic needs which may result in asbestos-induced burden in the near future. Lessons learned by industrialized countries are valuable indicators to implement effective policy and regulation to avoid any asbestos-related burden in this region.The past occupationalexposure to asbestoshas caused health risks and economic burden that should require well-prepared action plans to eliminate ARDs in Asian countries. Acknowledgment: This research was supported in part by a grant from National Research Foundation of Korea [2013R1A1A4A01011631]

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

S5. ASBESTOS MANAGEMENT AND MEDICO-LEGAL APPORACH TO ASBESTOS-RELATED DISEASES IN KOREA

Seung Hoon LEE Korea Environment Corporation, Environmental Research Complex Incheon, Republic of KOREA

Use of asbestos and products containing asbestos has been strictly prohibited in Korea because it has been scientifically proved that continuous use of them would cause malignant diseases, such as cancer. Workers who were exposed to asbestos in their working place are entitled to compensation under the relevant damage compensation act, but any asbestos health damage due to environmental exposure without involvement in asbestos-related work in the working place can be compensated since the enactment of the Asbestos Damage Relief Act in 2011. This Act has been established as a part of 「2009 Asbestos Control Comprehensive Plan」 promoted by the Ministry of Environment, Republic of Korea, and any victims of asbestos related disease (primary malignant mesothelioma, primary lung cancer, asbestosis, or pleural plaques) that may occur due to exposure to asbestos environment in Korea or the bereaved of victims can apply for relief pay under this Act.

This paper looks into matters to be considered with priority when introducing an appropriate asbestos damage relief system, such as an ultimate purpose of the Asbestos Damage Relief Act, beneficiary of damage relief and scope of application, method of decision on damage, raising relevant fund.

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

S6. A NOVEL METHOD FOR BETTER DIAGNOSSIS OF ASBESTOS-INDUCED LUNG CANCER (MESOTHELIOMA) FROM HUMAN BODY FLUIDS

Sherif ABBAS1, Dilek YONAR1, Nihal SIMSEK-OZEK1, Salih EMRI2*, Feride SEVERCAN1 1Middle East Technical University, Department of Biological Sciences, 06800, Ankara, TÜRKĠYE 2Hacettepe University, Department of Chest Diseases, 06100, Ankara, TÜRKĠYE

Malignant pleural mesothelioma (MPM) is an aggressive and rare form of cancer which arises from environmental fibrous minerals (tremolite asbestos or erionite) exposures. It is difficult to differentiate it from other lung cancers. Aim of this study is to develop a new method with high specificity and sensitivity for MPM diagnosis from body fluids (pleural fluids and serum) using Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy and chemometric analysis.

FTIR spectra of the samples collected from patients diagnosed with malignant pleural mesothelioma (MPM), lung cancer (MLC), benign (for pleural fluids) , and healthy ( for serum) controls (C) were recorded in the 4000-650 cm-1 spectral region. Spectral analysis indicated significant changes in the lipid, protein, carbohydrates, and nucleic acid contents in MLC and MPM with respect to the control samples. The significant variations in the saturated lipids, triglyceride/cholesterol ester content and lipid to protein ratio can be used as biosensors to diagnose MPM patients from pleural fluids. However, variation in the protein content and amide I to amide II area ratio were found to be used as biomarkers to diagnose MPM from serum samples. Hierarchical Cluster analyses (HCA) and Principal Component Analysis (PCA) were performed to differentiate the studied groups based on the spectral differences which revealed successful differentiation of the groups.

*This work was supported by the Scientific and Technical Research Council of Turkey (TUBITAK), SBAG-113S294 Research Fund.

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

S7. EXPOSURE, INTERNAL DOSE ANALYSIS AND ADVERSE OUTCOMES OF ENVIRONMENTAL POLLUTANTS IN HUMANS

Hilmi ORHAN Ege University, Faculty of Pharmacy, Department of Pharmaceutical Toxicology, 35100 Bornova, Ġzmir, TÜRKĠYE

One of the main obstacles in toxicological risk assessment is predicting the internal dose of the exposed chemicals in humans. Ethical reasons prevent experimental approaches such as obtaining tissue samples from living individuals. Although sampling from some tissues can be done in case of clinical obligations, it is usually impossible for the majority of tissues. The two possibilities are analysing the toxic outcome in unintentionally exposed cohorts in epidemiological studies, and measuring the concentration of the chemical directly in related tissues of cadavers. However, due to the huge variety of chemicals and toxic endpoints, surrogate parameters, so-called biomarkers, are measured in non-invasively provided biological samples. Among others, biomarkers should accurately reflect or correlated either to the toxic outcome, or to the concentration of the chemical of interest in target tissue. Such correlations are frequently sought in animal studies, although surgical tissue incision in humans offers a unique opportunity for such purposes. This lecture intends to document latest findings on exposure assessment and toxic outcomes of environmental pollutants in living systems, with the focus on addressing three major complex issues; (1) correlation between invasive and non-invasive sampling in animals, (2) biomarkers of internal dose, and (3) future perspectives of internal dose prediction in humans.

This study is supported by the Scientific and Technical Research Council of Turkey (TUBITAK) by the project numbers 108Y049 and 114S310, and Ege University EBILTEM project (2011BIL003).

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

S8. CHEMICAL WEAPONS FROM THE FORENSIC POINT OF VIEW

Ahmet AYDIN Yeditepe University, Faculty of Pharmacy, Department of Toxicology, Kayisdagi, Atasehir, Istanbul, TÜRKĠYE

Chemical weapons including lung damaging agents, cyanide, vesicants, nerve agents, incapacitating agents and riot-control agents have a long history in our world. They are toxic chemicals and cause serious health damages, capacity loss of individuals and death. They affect many individuals in the used area. For this reason they are called weapons of mass- destruction. They can use military purposes or terrorist attacks.

However Organisation for the Prohibition of Chemical Weapons (OPCW) has an exact position on the prohibition of the development, production, stockpiling and use of chemical weapons and on their destruction, the problem continues in some part of our world. Possible chemical weapon use have ben discussed in the offical and/or public documents or in media in places where conflicts are appeared. There have been some blurred information about the toxic chemical use in these places. The extentive analysis of victims in the problematic area can enlighten the real reason of death or serious health damage. Each toxic chemical used for mass destruction has a specific toxic and chemical characteristics. Their biotransformation in the living systems and interaction with biological compartments define their analysis in poisoned individuals. Toxic industrial chemicals (phosgene and chlorine), cyanide, mustard, lewisite, phosgene oxim, nerve agents, incapacitating agents (BZ, Fentanyl derivatives) and riot control agents (CS, CN, CR, and OC) were reviewed and current forensic analysis of these chemicals in poisoned casualties and environment were discussed in this presentation.

As a result forensic toxicology laboratories can review their capabilities and positions after a toxic chemical use for destruction of big masses.

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

S9. 2-CHLORO-1, 4-NAPHTHOQUINONE DERIVATIVE of QUERCETIN EXERTS ANTICARCINOGENIC ACTIVITY THROUGH the INDUCTION of and OXIDATIVE STRESS RELATED AUTOPHAGY in COLORECTAL CANCER

Shabnam ENAYAT1, MuĢerref S. CEYHAN1, Milan STEFEK2, Sreeparna BANERJEE1* 1Biology, Middle East Technical University, Ankara, TÜRKĠYE 2Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, SLOVAKIA

Phytochemical therapeutics such as Quercetin (Qc) have strong antitumor effects by inducing cell cycle arrest and apoptotic cell death, inhibiting enzymes activating carcinogens and modifying key signal transduction pathways. However, its clinical application is limited due to poor water solubility and low bioavailability. In a screening of novel semi-synthetic derivatives of Qc, 3, 7-dihydroxy-2-[4-(2-chloro-1,4-naphthoquinone-3-yloxy)-3- hydroxyphenyl]-5-hydroxychromen-4-one (CHNQ) was the most promising in terms of biological efficacy. Using a rat model of colitis, we have previously shown that CHNQ could ameliorate the effects of acetic acid induced acute colitis more efficiently that Qc. Since chronic inflammation very significantly contributes towards neoplastic transformation, we have hypothesized that CHNQ may also have potential as an anti cancer agent. Using colon cancer cell lines HCT-116 and HT-29, we have carried out detailed functional analyses comparing the anti-carcinogenic activities of CHNQ and Qc on cellular proliferation, cytotoxicity, cell cycle, apoptosis as well as autophagy and the associated signal transduction pathways. BrdU incorporation and cytotoxicity assays showed that CHNQ strongly inhibited cell

proliferation with an IC50 value of ≤ 20 μM, which was nearly 3 fold lower than the IC50 value of Qc (≥ 100 μM). Apoptosis was examined by Annexin V staining and flow cytometry, multi caspase activity assay and the expression of pro- and anti-apoptotic proteins using immunoblotting showing that treatment of cells with CHNQ resulted in a more robust induction of apoptosis compared to Qc. Treatment with CHNQ also resulted in the induction of oxidative stress as determined by the increased production of anions, leading to cell cycle arrest at G2/M. This was accompanied by the increased phosphorylation of MAP Kinases including; ERK1/2, p38 and JNK and decreased phosphorylation of Akt/PKB. Interestingly, the cells treated with CHNQ resulted in a dramatic increase in oxidative stress

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related autophagy as shown by increased expression and conversion of LC-3I to LC-3II, increased expression of Beclin 1, acidic vesicle accumulation and GFP-LC-3 puncta formation. All of these effects were also seen when cells were treated with Qc, however, the effect was weak and observed only at high doses. Overall, we propose that CHNQ, a semi- synthetic derivative of Qc, induces cancer cell death through the induction of oxidative stress and autophagy.

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

S10. POLYCYCLIC AROMATIC HYDROCARBONS AND THEIR TOXIC EFFECTS

Onur ERDEM Gulhane Military Medical Academy, Department of Toxicology, Etlik, Ankara, TÜRKĠYE

Polycyclic Aromatic Hydrocarbons (PAHs) are aromatic hydrocarbons with two or more fused benzene rings. They are ubiquitous and persistent chemicals that occur naturally in coal, crude oil and gasoline. The widespread occurrence of PAHs is largely due to their formation and release in all processes of incomplete combustion of organic materials. The last century of industrial development caused a significant increase of PAH concentrations in the natural environment. The general public may be exposed to PAHs found in soil/dust, air, water, food or household products. In addition, high exposure to PAH mixtures have been reported in several industries and occupations, including aluminum production, coal gasification, coke production, iron and steel foundries, diesel engine exhaust, coal tar and related products. Workers of these industries are continually exposed to different concentrations of PAH mixtures. These toxicants generate considerable interest, because PAHs are ubiquitous, some of them are highly carcinogenic in laboratory animals and have been implicated in breast, lung, and colon cancers in humans. Nonetheless, endogenous metabolic reactions of PAHs have an important role for occurrence of these toxic effects. The most common mechanism of carcinogenesis induced by PAHs is DNA damage through the formation of adducts. Alternatively, the presence of reactive oxidative species can also result with DNA damage. Benzo(a)pirene is the best known PAHs compound and used as a biomarker of exposure to PAHs. In conclusion, there will be made we will make a general assessment about PAHs in the lighting of the current knowledge.

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

S11. TOXICOLOGICAL AGENTS IN THERMAL AND DRINKING WATERS

Tahir NALBANTÇILAR Batman University, Department of Geology, TÜRKĠYE

People begin toxic metals to meet the intrauterine period and then breast milk and continue air of their braethe. Fetuses and infants in the process of rapid growth and development, have a greater sensitivity to the toxic effects of heavy metals than adults. In the case of adult humans, often shows an increase with the need for toxic exposure to air and water.

In the one of the most important causes of toxic factor exposures of people is water that the most important nutrient that feels as vital requirements. Water, which taken directly through mounth consumed each day, incorporates the water causes toxic effects of heavy metals.

The waters from geothermal fields is used for drinking or treatment because of its high mineral values. In addition, the water from the source, is mixed into the surrounding surface water and agricultural irrigation can be done with them. People are affected negatively directly or indirectly the combination. In this study, of water (drinking water and the thermal waters) toxicological significance is to be discussed, literature and empirical studies will be discussed.

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

S12. A NOVEL APPROACH FOR ENVIRONMENTAL BIOREMEDIATION

Rafig GURBANOV1*, Nihal SIMSEK OZEK2, Ayse Gul GOZEN2, Feride SEVERCAN2 1 Biochemistry Department, Middle East Technical University, 06800, Ankara, TÜRKĠYE 2Biology Department, Middle East Technical University, 06800, Ankara, TÜRKĠYE

Organic and heavy metal contamination are major environmental problem, whichleads to serious degradation in ecosystem. Traditional remediation techniques are based on physical, chemical and thermal methods. However, these techniques are very expensive, non-effective and labour intensive. Microbe-oriented methods generally known as bioremediationare proposed to be effective solution in remediation of soil, water and air. In these methods, microorganisms like bacteria, fungi and plants are commonly used. This is considerably new technology at development stage, which has several advantages as compared to the conventional ones like being economic and environmental friendly. However, the long-term decontamination period and lack of sustainability are the disadvantagesof bioremediation. Environmental factors such as pH, salinity, temperature etc. may negatively affect biosorption capacity of these microorganisms. There is a need for an accurate method for the discrimination of metal resistant microorganisms in order develop effective and sustainablebiosorption strategy. In the bioremediation literature, there is no rapid, accurate, reproducible and cost effective technique to screen and discriminate the heavy metal resistant bacterial strains from other strains. At this study, we aimed to develop a reliable method to identify and differentiate heavy metal resistant bacteria using ATR-FTIR spectroscopy together with multivariate analysis techniques such as HCA and PCA. Results of the study revealed that both control and metal exposed bacterial strains could be successfully discriminated from each other. This study shows that ATR-FTIR spectroscopy with chemometric analysis can be usedas a rapid and accurate method for the screening and diagnosis of microorganisms.

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

S13. POSTMORTEM ALCOHOL DETECTION

Gürol CANTÜRK Ankara University School of Medicine, Forensic Medicine Department, Ankara, TÜRKĠYE

Ethyl alcohol is the most commonly used and abused drug in the world. It has such numerous points of contact with medico-legal pathology that it has to be considered separately from all other substances. Body fluid ethyl alcohol levels can be reliably quantities in blood, vitreous humor, urine, breath, cerebrospinal fluid, saliva, and bile. The chronic abuse of alcohol leads not only to definite pathological changes in a number of target organs, but also contributes to deaths from neglect, hypothermia and burns.

Almost all alcohol is detoxified by the liver, only 2—10 per cent being excreted unchanged. The elimination mechanism is an oxidation of alcohol by liver enzymes, through acetaldehyde to acetate. The first stage is performed by the enzyme alcohol dehydro-genase but, as the second stage is much more rapid, little acetaldehyde has time to accumulate. The acetic acid is rapidly oxidized further to carbon dioxide and water. Death from alcoholic poisoning is not uncommon and can occur at blood levels in excess of about 300 mg/100 ml. Death can be caused either by the direct depressive effects upon die brainstem, mediated via the respiratory centres - or through secondary events such as aspiration of vomit. The absence of significant natural disease, injury or other toxicity, a high blood-alcohol level may reasonably be incriminated as the probable cause.

The basic standard in testing postmortem fluid ethyl alcohol levels for medicolegal purposes is whole blood (from femoral or subclavian veins) by headspace gas chromatography.

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

S14. CARBON MONOXIDE INTOXICATION AND ITS POSTMORTEM MARKERS

Birol DEMIREL Department of Forensic Medicine, Gazi University, Ankara, TÜRKĠYE

Carbon monoxide (CO) is a colorless, odorless, tasteless and non-irritating gas, because of these properties causing thousands deaths a year according to unofficial reports, that serious public health problem for our country. CO, usually occurs result of incomplete burning of substances that has unsaturated carbon. CO, is a by-product of the incomplete combustion of various substances with content of unsaturated carbon. CO is extremely toxic gas that is known to be used in the execution of a crime in ancient Greek and Roman. The affinity of hemoglobin for CO is more than affinity 200-300 times to oxygen. It is causes tissue hypoxia and eventually chemical asphyxial death occurs. These deaths are usually accidents. Suicide and homicide deaths rarely can be seen. In both cases, livings and death the most important diagnostic method is think about CO poisoning. Although difficult to diagnose in clinical cases, at autopsy, if autopsy technician sees cherry pink colours when 30% COHb (carboxyhaemoglobin) and pink colors on internal organs and soft tissues, autopsy technician knows the cause of death. Because of autopsy findings are nonspecific, definitive diagnostic method is measuring the amount of COHb in blood and various tissues. COHb is quite stable and can detect even a long time after the death. Blood gas analysis is sufficient to make the diagnosis in most cases. Gas chromatography, which measure CO amount in internal organs, muscle and even bone tissues, should be used in severely burned bodies that could not taken blood.

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

S15. NARCOTICS AND POSTMORTEM PROCESS

Taner AKAR Department of Forensic Medicine, Gazi University, Ankara, TÜRKĠYE

The term narcotic was initially used to connote the opioids. In its current use the term to indicate any illicit psychoactive substance. Toxic substance is any substance which when absorbed into the blood seriously affects health or destroys life. Drugs may be absorbedorally, by intravenous, subcutaneous orrarely intramuscular injection, by smoking or by nasal sniffing.

The routine at autopsy, in respect of obtaining samples for toxicological analysis, is altered according to the route of administration. For example, if drugs may have been taken by nasal route, such as cocaine and heroin, then dry swabs from each nostril should be taken. When poisoninig is suspected, or when no gross pathological process has been found at autopsy to adequately explain the death, it is mandatory for specimens to be taken for toxicological analysis, each specimen must be retained in a separate, properly cleaned and sealed container. These must be identified and labeled with the case number, the name of the deceased and the date, time taken and site of collection. The specimens must be taken be fore autopsy so as to avoid contamination. Biological fluids and tissues taken prior to death must also be retained and submitted for analysis. Antemortem blood specimens taken on admission to hospital are more relevant in persons taking hours or days to diethan are those taken at autopsy.

No matter how good one‘s toxicology laboratory, it cannot function if there is failure to collect the proper specimens, in adequate quantity, and in the proper conditions.

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

S16. TOXICOLOGIC PATHOLOGY

Sultan PEHLIVAN Council of Forensic Medicine, TÜRKĠYE

Poison and poisoning is important terms for forensic science. Shortly, toxicology is defined as poison science. Forensic Toxicology which is a sub-unit of toxicological studies n forensic toxicology is used of poisoning and poisons work justice application.

Toxicity, which bases on structure, features and dose of chemical type, is a relative term. Mode of action and toxicity effect‘s speed is important in the development of the morphological changes. When the history is unknown, histologic findings may be directed to the toxicological examination.

All of the histological changes occurring in the postmortem process poisoning are nonspecific. Both autopsy and histological examination may be inconclusive in the investigation of the poisoning findings.

Postmortem examination of poisoning cases investigated involves the integration of histological organ case in the evaluation of toxic damage to tissues, generally to a direct toxic effect or can‘t be considered proven to be responsible for the owned indirectly cause a lesion. Evolution of histological findings indicated that poising must be evaluated in connected with this situation in mind. Therefore this evaluation is important to limit the momentous and reliable findings.

In this study, in suspected cases of death, the importance of determining the cause of death of the toxicological effects. Induced histopathological findings will be discussed.

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

W2. INDIVIDUAL SUSCEPTIBILITY TO XENOBIOTICS, BIOMONITORING AND KINETIC DATA: A HELP FOR FORENSIC MEDICINE

Emanuela TESTAI Istituto Superiore di Sanità- Mechansism of Toxicity Unit Viale Regina Elena, 299 00161 Roma ITALY

The quantitative assessment of exposure to chemicals able to induced fatal outcome in humans as well as the time course of exposure is essential information also in forensic medicine. Generally, only the extent of the external exposure is available, although it is recognized that measuring internal exposure is much more relevant for establishing a dose- response relationship. Starting from external exposure, the estimate of the internal one depends on availability of information about the absorption, distribution in the body, metabolism and excretion (ADME) of a chemical, usually referred to as toxicokinetics (TK).

Many of the enzymes and transporters involved in the biokinetics of a chemical are polymorphic, varying among individuals, thus resulting in different individual susceptibility to xenobiotics. The activity of specific enzymes can differ also due to exposure to chemicals since many of them are inducible or can be irreversibly inhibited. As a consequence the effects of a xenobiotic may be highly dependent on both genetic and aquired factors. Biomonitoring studies on humans are very important tools to determine ‗internal‘ exposure, but the TK should be taken into consideration when using biomarkers of exposure, as they reflect also the individual‘s response and when translating level in blood or urine to an external dose (or vice-versa). In addition, the monitoring strategy should be based on the TK of the chemical: sample collection time-points, sample type (urine, blood or other) analyte to be determined (parent compound or metabolite) and numbers of individuals sampled strictly depend on ADME parameters.

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

S17. IDENTIFYING BIOMARKERS OF ARSENIC EXPOSURE AND METABOLISM IN HUMAN URINE THROUGH SPECTROSCOPIC TECHNIQUES

Parvez I. HARIS De Montfort University, The Gateway, Leicester, LE1 9BH, UK

Our understanding of molecular changes associated with exposure to arsenic is poorly understood despite the fact hundreds of millions of people are exposed to this toxic element. Spectroscopic analysis of human biofluids from people exposed to arsenic can help identify biomarkers of arsenic exposure which can be valuable for diagnostic purposes and also for understanding biochemical changes induced by arsenic. Our methodology involves collecting and analysing urine samples from populations that are exposed to arsenic through their diet and drinking polluted water. The volunteers providing the urine samples are asked to complete a questionnaire on demographic characteristics, diet and life-style factors. Subsequently, the urine samples are analysed using different spectroscopic methods including ICP-MS, MALDI-TOF, FTIR and NMR spectroscopy. The talk will present data on urinary arsenic and its metabolites (determined using ICP-MS), associated with arsenic exposure from water and foods, and their relationship with other metabolites and macromolecules determined using MALDI-TOF (proteins), FTIR (proteins and other macromolecules) and NMR (metabolites) spectroscopy. For example, our NMR study revealed that urinary arsenic was significantly correlated to %dimethylamine (r =0.169, P=0.044) in a Bangladeshi population that is exposed to high concentration of arsenic through drinking contaminated water. The lecture will also present data which demonstrates human exposure to arsenic from consumption of rice in people from the United Kingdom and Bangladesh. For the population in Bangladesh, an increase in skin lesion prevalence (P-trend=0.007) and skin lesion incidence (P-trend=0.07) was associated with increased intake of steamed rice.

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S18. ARSENIC EXPOSURE AND THE RISK OF PRECLINICAL AND CLINICAL ENDPOINTS OF CARDIOVASCULAR DISEASE

Yu CHEN Departments of Population Health and Environmental Medicine, New York University School of Medicine, USA

Epidemiologic studies have linked arsenic exposure from drinking water to elevated risks of cardiovascular disease (CVD). However, prospective studies are lacking, and the underlying mechanism by which arsenic may lead to CVD is unclear. We conducted a series of cross- sectional and prospective analyses using data from the Health Effects of Arsenic Longitudinal Study (HEALS) in Araihazar, Bangladesh, involving more than 20,000 participants. We found that chronic arsenic exposure from drinking water was positively associated with the risk of fatal and fatal cardiovascular disease, especially in those with high levels monomethylarsonic acid in urine or smokers. There was a positive association between arsenic exposure with plasma levels of sVCAM-1 and the association was stronger in people with higher body mass index. In addition, past long-term arsenic exposure was related to subsequent QT-interval prolongation, especially in women. Arsenic was also related to higher levels of intima-media thickness, an early marker for atherosclerosis. Our results indicate that mechanisms underlying arsenic exposure-related CVD may involve inflammation, endothelial dysfunction, electrocardiogram abnormalities, and incomplete arsenic methylation capacity.

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1st INTERNATIONAL CONGRESS & WORKSHOP of FORENSIC TOXICOLOGY Ankara-TÜRKİYE November 29-30, 2014

S19. GENETIC SUSCEPTIBILITY IN ARSENIC TOXICOKINETICS

Dilek KAYA-AKYÜZLÜ, Zeliha KAYAALTI Ankara University, Institute of Forensic Sciences, Ankara, TÜRKĠYE

Metalloid element arsenic is a widespread environmental toxicant and various forms of arsenic present in the air, water and soil due to natural and anthropogenic activities. The inorganic forms of arsenic (iAs), arsenite and arsenate, are the most toxic chemical species found in food and water. Human can expose arsenic mainly via drinking water and food supply. The other source of arsenic is the occupational exposure. Arsenic exerts its toxic effects on various tissues by binding to sulfhydryl groups of proteins. Acute and chronic exposure to arsenic is known to lead to non-cancer health effects and various cancer types including skin, bladder, liver and kidney. However, individuals and populations show differences in susceptibility to arsenic-related diseases and cancers due to the variations in arsenic metabolism.

In the human body, arsenic metabolism consists of a series reduction and methylation processes, and the main proteins and enzymes of this metabolism are glutathione S- transferases, arsenic (+ 3 oxidation state) methyltransferase (AS3MT) and multi drug resistance associated proteins (MRPs). Genetic variants in these proteins and enzymes due to polymorphisms have been shown to be related with different urinary arsenic metabolism patterns. Previous studies have shown that individuals who metabolize arsenic poorly may have higher risk for developing arsenic-related diseases and certain cancers than individuals who metabolize arsenic well.

In this study, some specific genetic polymorphisms in genes encoding proteins and enzymes involved in mechanisms of arsenic metabolism and their effects will be mentioned.

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S20. MINING POLLUTION IN TURKISH REPUBLIC OF NORTHERN CYPRUS: AN OVERVIEW

Fezile ÖZDEMĠR TURKISH REPUBLIC OF NORTHERN CYPRUS (TRNC)

Cyprus has long been known as an island with copper resources. In fact, it is said the name of Cyprus is derived from the word Cyprium and Cuprium means Copper. The Cyprus Mining Corporation (CMC) made a major contribution to the Cypriot economy until 1975. Due to events of the war in 1974, the company abandoned mining in the area in 1975. Over the years, without any environmental protection measures of the mining area being undertaken, contamination caused by what remains there is more severe than previously estimated. Several reports have shown that soil, drinking water and irrigation water are contaminated by heavy metals. Also living organisms are affected such as crops, plantlife, and animals, as well as human populations. Along with Cyprus, it is believed that other eastern and middle Mediterranean countries are endangered too. In this overview, contamination of the environment, living organisms and public health problems will be presented, along with the legal status of the CMC in relation to European Environmental Policy and the Constitution of the Turkish Republic of Northern Cyprus, in accordance with previously conducted research.

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S21. HISTORY OF CLINICAL RESEARCHES AND ETHICAL COMMISSIONS IN OUR COUNTRY AND WORLDWIDE

Hilal ĠLBARS Turkish Medicine and Medical Device Agency, TÜRKĠYE

Drug investigation sand treatment methods on humans dates back to very early times. The oldest records about clinical research was done by the King of Babylon, Nebuchadnezzar, in 562 BC. The first trial of a new a treatment was done in the Renaissance period by the surgeon Ambroise Pare in 1537. According to many sources, use of a control group in experiments was first practiced by the father of clinical trials James Lind. In 1800's clinical trials have started to spread giving more importance to study design. In 1803 Thomas Percivalin "Code of Medical Ethics" advised on conducting research ethics. When we look at the history of clinica lresearchs it is known that errors are found, even causing fatal events. Examples to such events in the history are as follows: The pseudo-medical experiments conducted by 23 German medical doctors on thousands of prisoners with out their consent who were accused of killing them led to the publication of the Nuremberg Code in 1947. The Tuskegee study which started in May 1932 ended in 1972, the Willowbrook study which was conducted between 1963 and 1966 period, and the Jewish Chronic Disease Hospital study which was done at 1963 are other prominent examples of the past. In order to prevent such incidents and establish necessary legal arrangements as well as to protect the rights, health security and well being of volunteers who participate in researchs, the establishment of independent committees called as ethic committee in the World which are responsible from giving opinions in respect of scientific and ethical aspects of the research can be summarized as follows: the publication of ―Medicine Morality Guideline‖ in Canada in 1971; the establishment of a committee in 1976 in the US state of New Jersey;the establishment of a bioethics committee in 1977 Montefiore Medical Center in New York; the increase in the demand for ethic committees due to the recommendation of the World Medical Association in 1975 to regulate researchs on humans, the first conference regarding hospital ethic committees which was held in the Washington state in 1983. InTurkey, clinical research ethic committee was first introduced in 1993 by the "Regulation on Drug Research‖which has been updated in 2014. In addition to this, there are also guidelines which regulate working procedures and principles of ethic committees.

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S22. ETHICAL and LEGAL REQUIREMENTS in CLINICAL RESEARCH

Nihat VAROL, Judge Ankara 8.Ağır Ceza Mahkemesi Üyesi

Aging in our world of medical materials used in the treatment of deteriorating health, alongside the development and the protection of human health (medicine, method, etc.), the presence of legal until the presence of in obtaining medical procedures process an extremely sensitive issue.

Methodology of clinical research, patient participation in research, the results of the review and policy in transforming the social benefits of information obtained; must be at least damage the highest interest.

Medication is actually a poison. The dose is the determining factor here. Accordingly, applying the nature of the benefit or harm people determine the responsibility of the dose. But how it should be implemented in dose should be determined with absolute pre-clinical research, while this research, "Medical Ethics" appropriate while "Proper Law" also has to be.

Law determining factor in eligibility, rights in accordance with the standards of medical and health professionals to fulfill the duties and processing the exposed person to (patient / solid) is to consent to these transactions. This rule is a legal requirement. Standards are subject to legal evaluation with both breach of contract and tort causes.

Essential health services; accordance with the law, in the form required by the profession initiative is based on teamwork.

Legal aspects of clinical research in this context has been drawn. they are;  Application of Biology and Medicine Respect for Human Rights and the Convention on Protection of Human Dignity: Human Rights and Biomedicine Convention Concerning the Approval of Assent Act No. 5013 (Date of Admission: 03/12/2003) RG09.12.2003- 25311  Patients' Rights Directive (RG: 01.08.1998 -23 420)

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 Regulation on Clinical Trials of Pharmaceutical and Biological Products (RG: 13.04.2013-28617) (worth it. RG: 25/06/2014 -29 041)  5237 Turkish Penal Code (OG: 12.10.2004- 25611)

This case will be illustrated with examples of violations of the legal aspects of the conference what we encounter.

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S23. NATIONAL AND INTERNATIONAL LEGISLATIONS ON CLINICAL RESEARCHES

Asım HOCAOĞLU Turkish Medicine and Medical Device Agency, TÜRKĠYE

The development of new treatments against diseases is only possible with clinical trials. However this struggle may be lead to abuses that acts endangering human dignity, to guarantee the dignity of the volunteers who participated in the research and also believed that both individuals and volunteers are needed to respect as a member of the human kind, there are made various legal regulations at international and national level.

In this presentation, these regulations will be referred and also aimed to give information about biomedicine agreement, the Declaration of Helsinki and the Turkish Criminal Law Article 90.

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W3. THE KNOWN UNKNOWNS HIGH PRODUCTIVITY FORENSIC SCREENING of UNKNOWNS WITH MORE CONFIDENT IDENTIFICATION

Sebastian BROECKER Agilent

Due to the large variety and the steady increase of toxicologically relevant substances, systematic toxicological analysis (STA) is one of the most difficult tasks in analytical chemistry and, therefore, a steady topic of research and methodical improvement. For this reason, the suitability of liquid chromatography in combination with hybrid quadrupole time- of-flight mass spectrometry (LC-QTOF-MS) for STA was investigated. For this purpose, a database of more than 9000 and a CID spectra library of more than 3000 toxicologically relevant substances and suitable methods for sample preparation were developed. The application was evaluated at spiked blood, urine and hair samples. It was found that the analysis in Auto-MS/MS mode (alternating measurement cycles of MS and MS/MS spectra) allowed substance identification in all investigated biological matrices using CID spectra. The suitability of LC-QTOF-MS for STA was tested for hair samples from 30 drug-related death cases and from 60 death cases with known chronic medication as well as for 77 blood samples. For the search of metabolites, a metabolite tool was developed. In the practical application to data files from blood, urine and hair samples, the tool proved to be very helpful for identification of unknown peaks and for confirmation of results obtained only from the database without CID spectra. A tool "Estimate Concentration" was created for automatic estimation of concentrations of identified substances. The application to real blood and hair samples and the comparison of the concentrations with results from HPLC-DAD and GC-MS showed good agreement. Overall, these investigations showed that LC-QTOF-MS is currently the most favorable method for STA. Because of the comprehensive registration of all substances in a sample, the data files can be checked for the presence of certain poisons even later without new measurements.

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S24. LABORATORY ANALYSIS AND FACTORS AFFECTING THESE ANALYSES IN POSTMORTEM TOXICOLOGY

Mukaddes GÜRLER Hacettepe University, Department of Medical Biochemistry, Ankara, TÜRKĠYE

Postmortem toxicology which is the part of Forensic Toxicology deals with the analysis of alcohol, drugs, illicit drugs or other poisons may have caused or contributed to the death. Postmortem toxicology differs from clinical toxicology (therapeutic drug monitoring) and emergency toxicology, which deals with the living patient.

Postmortem toxicology is an especially complex area since many factors may influence the interpretation of the results obtained. Possible factors may be related to: (a) the nature of the poison(s)/drug(s) present; (b) sample type, collection, transport and storage; (c) the analytical methodology used; (d) the circumstances of exposure; (e) mechanical factors such as trauma or inhalation of stomach contents; (f) pharmacological factors such as tolerance or synergy; (g) history of the case; and (h) postmortem changes (redistribution and incomplet distribution of drugs, decomposition of the body).

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S25. ENTOMOTOXICOLOGY

Ersin KARAPAZARLIOĞLU Faculty of Security Sciences, Turkish National Police Academy, Ankara, TÜRKĠYE

Insects can be used to estimate a PMI (Post Mortem Interval) by applying the known developmental rates of insects and the successional patterns of different insect species on the dead body. Insects feed decomposed tissue and life stage of insects can be affected by contents of these tissues if it has some toxic material. Investigating the infected insect specimens also show concentration of toxic substances. Typical postmortem specimens for a toxicological analysis include brain, liver, kidney, heart blood, peripheral blood, vitreous humor, bile, urine, and gastric contents. In some cases, the tissue samples are rendered unsuitable for analysis, or they are simply no longer present in the body. Therefore, in these cases, alternative specimens often need to be examined. Properly preserved or freshly collected larvae and other insect forms can be treated as any other tissue for toxicological analysis.

Entomotoxicology is a relatively new branch of forensic entomology. Diptera and other arthropods can be reliable alternative method for drug detection in decomposed body.

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S26. THE IMPORTANCE OF SOIL IN POSTMORTEM TOXICOLOGICAL ANALYSES

Murat MERT Council of Forensic Medicine, Ankara, TÜRKĠYE [email protected]

Body decomposition and putrefaction start by death. In cases of suspected poisoning, samples such as body fluids, blood, urine, organs, bones and stomach contents are used for toxicological analyses in both antemortem and postmortem periods. However, during toxicological analyses of high-degree decomposed or totally decomposed graved corpse, it is also important to analyze soil samples contacted with corpse to detect toxic substances toxic material analyses from corpse contact soil is very important.

In graved corpse, body fluids transported to contacted soil with decomposition. At this stage, since toxic substances in the body are also transported to soil in time, corpse originated toxic substances can be detected how much time passes.

There are various burial mechanisms in different societies according to their life style and religious. While the bodies are burned in some societies, coffin is impregnated with process in some societies. In Muslim society, bodies are buried after shrouding with ―white shroud‖ . These types of burials are the main topic of our studies.

In this study, the importance of soil in toxicological analyses of graved corpse, how the soil samples should be collected for toxicological analyses and analyses methods in soil toxicology will be presented with present cases.

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S27. IS THERE A NEED FOR FORENSIC PHARMACOVIGILANCE AS A SPECIALTY?

Semra ġARDAġ Marmara University, Faculty of Pharmacy Toxicology Department, Drug Safety and Pharmacogenetics Unit, Istanbul, TÜRKĠYE

Forensic science is the application of a broad spectrum of sciences to answer questions of interest to a legal system which are related to crime. The increase in the number of court cases examining and addressing problems with medicinal products seems warrant a discrete sub- discipline of forensic pharmacovigilance and creates the issue whether there is a sufficient specialism within the existing area of forensic pharmacology / toxicology. Forensic pharmacovigilance uses the expert knowledge of adverse drug effects, or any other drug related problems, to resolve legal questions and to detect or uncover criminal acts. In the context of the criminal courts, perhaps the most frequent examples are crimes related to medications that result in adverse effects; i) alleged neglect or failure to inform patient about the potential harm, prescribing, preparation, dispensing or administration, ii) in the manufacturing of drugs (counterfeiting, contamination and quality production) .Such situations often require opinions by independent experts. In order to initiate a debate, the lawyers should understand what PVs can and should do to assist the court in assessing evidence of drug effect and its varying quality. The above discussion is taken from the International Society of Pharmacovigilance (ISoP) meeting where the group concluded that the forensic pharmacovigilance as a speciality is necessary with raised health professionals to act objectively, to realise all evidence in the context of the court enquiry. In this talk, an outline of the role of pharmaceutical toxicologists with a forensic pharmacovigilance perspective in this process will be discussed.

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S28. EVALUATION OF POTENTIAL ENDOCRINE DISRUPTING EFFECTS OF HERBAL DIETARY SUPPLEMENTS

Hande GURER-ORHAN, Yasemin TOKER, Duysal USLU, Ozlem YILMAZ-DILSIZ, Altug YAVASOGLU, Erdal BEDIR Ege University, Faculty of Pharmacy, Department of Toxicology, Bornova, Ġzmir, TÜRKĠYE

Endocrine disrupting (ED) chemicals are suggested to be involved in global decrease in semen volume and sperm counts, increase in urogenital abnormalities, rate of testicular cancer in males and breast cancer in females. Mainly synthetic ED compounds are blamed for those adverse effects while phytoestrogens are mostly known for their beneficial health effects. Phytoestrogens have been safely consumed traditionally in the Asian diet for many years. However nutritional and pharmaceutical use of these compounds has dramatically increased over the last decades by the Western population. Recent studies reported that phytoestrogens can be hazardous when exposed at susceptible life stages and administered late in life. The present study is undertaken to screen the potential ED effect of widely used herbal dietary supplements in Turkey. Binding affinity of the selected products to estrogen receptor was evaluated by a ―receptor binding assay‖ and their potential estrogenic or antiestrogenic effect was evaluated via a cell based in vitro assay, E-Screen. Aromatase inhibiting activity of the dietary supplements was evaluated in vitro. Finally the in vivo ―uterotrophic assay‖ was performed to confirm estrogenic effect found in in vitro assays. Another aim of the present study is to determine and quantitate the phytoestrogen content (genistein, daidzein, glycitein, formononetin, biochanin A and coumestrol) of the active dietary supplements found in screening assays. Toxicological risk assessment is performed in four steps: hazard identification is the first step where the toxic effect of a compound is evaluated. Exposure assessment is another step where estimated daily exposure is evaluated. The present study provides data to both steps of toxicological risk assessment of the selected herbal dietary supplements.

This study is supported by the Scientific and Technical Research Council of Turkey (TUBITAK) by the project number 108S202 and Ege University EBILTEM project (09-BIL- 033).

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S29. DRIVING UNDER THE INFLUENCE OF PRESCRIPTION AND OVER-THE- COUNTER DRUGS

Munevver AÇIKKOL, Selda MERCAN Istanbul University, Institute of Forensic Sciences, Forensic Toxicology Laboratories, 34303, Cerrahpasa, Istanbul, TÜRKĠYE

Prescription drugs are sold to the consumers with a prescription by a doctor. Non prescription drugs are sold without a prescription and are also referred as the over-the-counter (OTC) drugs. Driving under the influence of medications and drugs is one of the important risk factor for traffic safety. Prescribed or OTC drugs effect on the activity and function of the central nervous system may impair driving ability.

Tranquilizers (benzodiazepines), hypnotics (pentobarbital sodium), analgesics/pain killers (opioids such as oxycodone, hydromorphone), antidepressants (fluoxetine), stimulants (methylphenidate), tricyclic antidepressants (TCAs), antihistamines (diphenhydramine, chlorpheniramine), centrally acting muscle relaxant (carisoprodol), are the most hazardous drugs for traffic safety.

Recently, scientists, politicians and societies as a whole have begun to question the extent to which medicines and drugs contribute to traffic accidents, and what can be done about it.

Not all medicaments, even those in the same therapeutic group have the same effects on driving ability. A proposal has therefore been made to classify medicaments into three categories by (CPMP III/9163/90-EN). The performance related to driving or using machines, specify whether the medicinal product has (a) no or negligible influence (b) minor or moderate influence or (c) major influence on these abilities.

As a result, more effort must be made as much as possible by authorized organizations to avoid or reduce the occurrence of traffic accidents due to prescription and over-the-counter (OTC) drugs.

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S30. TOXICOLOGICAL APPROACH TO INDUSTRIAL EXPOSURE: WHERE ARE WE?

Engin TUTKUN Ankara Occupational Disease Hospital Ankara, TÜRKĠYE

A large number of working people are injured, become ill or die world wide every year, as a result of chemical exposure at work. From the occupational health point of view, the main problem in the work place is wide and unsafe use of toxic chemicals, especially in small and middle-scale work shops. In all countries, the Occupational Health and Safety (OHS) Systems aim to prevent and control occupational exposures by the help of different measures, including education, inspection and engineering controls. The main barriers to prevention is cost, time, insufficient man power, sociall pressures, technical barriers, individual right sand lack of education. Information and awareness on how toxic chemicals pose risk to human health is the main step in controlling health risks of toxic exposure in the work place. For this reason, the strength of toxicology-related sciences in the area is the main promoter in the solution of this problem. In Turkey, insufficiency of diagnosis of occupational diseases and statistical determination is the under lying etiological factor in low number of occupational patients. In this case, toxicology, as one of the main instruments of occupational health‘s determinants, is normally out of focus. There is approximately 19.000.000 registered working population in Turkey and Social Security Institute have announced only 77 compensated patients due to toxic exposures in the work place in 2012. These numbers do not reflect the truth. It is obvious that OHS system should be re-designed quickly and the first step should be improving the art of ―toxicological approach to toxic industrial exposures in the work places‖.

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S31. THE LABORATORY APPROACH TO WORKERS EXPOSED TO XENOBIOTICS

Ceylan BAL Ankara Occupational Disease Hospital, Ankara, TÜRKĠYE

Exposure to toxic substances in the workplace is increasing due to improvements in the industrialization. When compared with the first decades of this century, it has been known that types and numbers of toxic substances in the workplace has increased enormously in recent years. This also has become an environmental problem, besides occupational health problems. In terms of occupational health and safety, determination of toxic substance is mainly carried out by air monitoring. Exposure to toxic substance can also be determined by analysis in biological samples such as blood and urine. It is important to determine that source of exposure is the workplace. On the other hand, severity of exposure can be evaluated according to different guidelines of various organizations like American Conference of Governmental Industrial Hygienists (ACGIH). But still, there is no consensus about some exposure types, like manganese, yet.

Time of sampling, sample type, selection of method and interpretation of results are major determinants of monitoring the workplace. Samples should be taken at the end of work shift and should be analysed as quickly as possible. Urine samples are mostly ideal for solvents while urine, whole blood and serum can be used as biological samples for metals‘ analysis. Methods should be selected according to substance variety and detection limits. Results should be interpreted according to types of substances which the workers have been exposed, duration of exposure and biological exposure limits.

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S32. ARE MOST OF CHRONIC DISEASES REALLY IDIOPATHIC? EXPOSURES AND CHRONIC DISEASES

Uğur KARAKULAK Ankara Occupational Disease Hospital Ankara, TÜRKĠYE

Idiopathic simply means that no cause can be determined for a medical condition. Some common diseases such as pulmonary fibrosis, thrombocytopenic purpura and portal hypertension, remain idiopathic, meaning that despite their frequency physicians have not been able to determine their etiology, underlying mechanism and what triggers them. While physicians and researchers have an enormous amount of information about disease and the human body, many conditions are affected by a range of factors, making it difficult to pinpoint a specific cause. Additionally, much remains to be learned about the causes of many conditions. At this point, during disease management in clinical practice, clinicians mostly focus on conventional risk factors and etiologies. Almost every day most of people expose several life threatening factors both in daily life and working life. A wide variety of materials that have a part in our lives such as fluorescent lamps, thermometers, batteries or insecticide, can play role in the etiology of many diseases that we describe as idiopathic. In this presentation, the relationship between chronic diseases as known idiopathic and exposure to heavy metals, toxic and chemical substance will be discussed.

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POSTER PRESENTATIONS

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P1. THE CELLULAR MECHANISM OF MERCURY NEUROTOXICITY AND A CASE REPORT

Murat BÜYÜKġEKERCĠ 1*, Erol Rauf AĞIġ1 1Department of Pharmacology, Ankara Occupational Diseases Hospital, TÜRKĠYE *[email protected]

In vitro and animal studies performed in the last 40 years revealed that the neurotoxicity induced by Methylmercury (MeHg) involves a) depletion of intracellular antioxidants b) inhibition of critical enzymes c) modulation of transporter activity and neurotransmitter receptor activity. As a long term effect MeHg is reported to modify gene expression and change the cellular signalling. The neurotoxicity mechanism of MeHg mainly depends it‘s electrophylic property, as it reacts with low and high molecular weight proteins possesing thiol and selenol groups. This reaction is partly responsible for the depletion of anti-oxidant capacity and accumulation of reactive oxygen species. Oxidative stress which is defined as the deterioration of the equilibrium of pro-oxidant/anti-oxidant in favor of pro-oxidant state plays the major role in MeHg induced toxicity. As a result of the interreaction with thiols and selenols the intracellular Ca concentration is modulated and neurotransmitter release is either inhibited or augmented. MeHg also increases the intracellular Ca concentration via raising the extracellular levels of glutamate. MeHg induces the deterioration of glutamate homeostasis by reacting with the glutamate receptors at synaptic vesicles and plasma membranes. It shows higher affinity to seleno groups than thiol groups. Because of that MeHg binds to specific thiol groups but also binds more stably to anti-oxidant selenoproteins like glutathione peroxidase (GPx) and thioredoxin reductase (TrxR). GPx and TrxR are inhibited following MeHg exposure. Inhibition of these selenoenzymes (perhaps degeneration of other selenoproteins) is the primary pathway of MeHg induced oxidative stress.

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P2. THE FORENSIC DEVELOPMENT IN TAIWAN

Chang-En PU Vice President, Taiwan Academy of Forensic Science (TAFS), Taiwan, ROC

Scientific and technological methods are extensively executed in crime scene investigations which are entrusted from various levels of judicial organizations in Taiwan for seeking out the corpus delicti.

By augmenting new high-tech devices, training forensic scientists, applying ISO 17025 guide- lines and emphasizing R&D, the forensic society has been honored with valuable public praise in arena of scientific examination and identification at both home and abroad.

Besides 4 main forensic science laboratories, Universities (like Central Police Univ.), Accreditation Organization (Taiwan Accreditation Foundation-TAF), Taiwan Academy of Forensic Science (TAFS), The Henry C. Lee Forensic Science Foundation, and Journals all work together to form the forensic society and through positive interaction thus enhance the capability of the society, then accordingly strengthen the quality of the law enforcement and judicial system.

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P3. THE FORENSIC TOXICOLOGY OF MJIB IN TAIWAN

San-Chong CHYUEH* Investigation Bureau, Ministry of Justice, Taiwan, ROC *[email protected]

The chemical analysis laboratory, also named institute on Drug Abuse, Investigation Bureau, Ministry of Justice (MJIB), is the first drug testing laboratory accredited in respect of ISO/IEC 17025 in Taiwan. The chemical analysis laboratory is responsible for criminal evidence identification via chemical analysis, clandestine lab analysis, drug metabolite analysis, counterfeit medicine analysis, protected wildlife product analysis, and other chemical analysis. Drug urine and drug hair analysis are the main works of forensic toxicological identification in our laboratory. The recent developments on drug urine and drug hair analysis of MJIB in Taiwan are introduced in this poster.

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P4. FORENSIC ENTOMOLOGY AND MITES

AyĢe YEġĠLAYER*, Eyüpcan MATUR GOP University, Tokat, TÜRKĠYE *[email protected]

Mites are too small and they can be found many habitat including plant, forest, water, housedust, stored food and corpse even. The smell of carcass, after firstly flies and phoretic mites are comes to dead body. Mites are live specific habitats so that death can be use dead time or movement of bodies is detected on forensic entomology. Mites are analyzed to crime cases as a indicator and can be provide evidence solving for crime also. i.e. homicides or suicides. In addition toxic substances in a corpse and drugs affect the rate of development of pest stages, in this way easily estimate criminal investigation. In some studies mite and ticks are found infesting dead bodies and belonging to Astigmata (Acarussiro L., Acarusfarris (Oudemans) and Tyrophagusputrescentiae (Schrank)) species are reported on human carcasses or carrion. Researchers are found A. siro can ocur in the later stages of body decomposition. In fact this species pest of stored foods and have been collected as a phoreticdeutonymphs from carcass. Some mites species have known specific relationship Dermestes and Coccinellid beetles. Consequently ıt is neccessarymany investigation about mites for helping solve to crime and must be increased cooperation between specialist (acarolog, entomolog) with forensic department.

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P5. TOXICAL EFFECTS OF PESTICIDES ON DAILY LIFE

AyĢe YEġĠLAYER1*Nihat YEġĠLAYER2 1GOP University, Faculty of Agriculture, Deraprtment of Plant Protection, Tokat, TÜRKĠYE 2GOP University, Faculty of Aquaculture, Tokat, TÜRKĠYE *[email protected]

In our daily lives, use of pesticides which may cause detrimental effects on microand macrofauna of soil and water. Mites and insects are controlled with pesticides in agricultural land and landscape areas. Pesticides are used in practice some of broad spectrum and others specific; can affect food chain, fish, benefical mite and insects, soil, water and human health. After the control that chemical pesticide are accumulated soil and water and it can be harmful in here. There are many research papers in literature on to natural enemies insects and fish are killed by pesticides. Pesticides are caused elimination of many rare species of fish and natural enemies mite and insects populations. Also some pesticides are known extremely toxic to most aquatic organism and also tocheyletidae, phytoseiidae (Acarina) mite families. Additionally, ın the recent years many human illness and deaths have occurred as a result of exposure to pesticides. Small residues of pesticides, suspected of being carcinogens, in drinking water and food. Finally, pesticides are caused adverse environmental impact in agricultural landscapes, soil and water. Therefore landowners and practioners should be restriction pesticides, Integrated Pest Management (IPM) should be applied controls with limited pesticide use to keep pest populations below economically damaging levels, prevent future pest problems, and minimize the harmful effects of pesticides on humans and natural resources, including wildlife.

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P6. TRADITIONAL MEDICINE: ANTIBACTERIAL ACTIVITY OF Tagetes minuta PLANT LEAVES EXTRACTS

Abdulkarim UZABAKIRIHO Ankara University, Institute of Forensic Sciences, Ankara, TÜRKĠYE [email protected]

Medicinal plant is the weapon used by Rwandan people especially those of rural areas to heal different diseases but sometime the usage does not refer to any scientific proof. This Project was focused on the antibacterial activity determination of Tagetes minuta plant leaves extract. Antibacte-rial activity was carried out using Escherichia coli, and Staphylococcus aureus. Water and methanol was used in extraction as solvent. The activity was evaluated at different concentration by using disc diffusion and serial dilution methods. Methanol extracts had stronger inhibitory effects on both bacteria while the aqueous extracts didn‘t showed any effect on both bacteria and the most susceptible bacteria in this study were S. aureus than E. coli. The antibiotic penicillin shows greater inhibition zone than that of plant extracts.This study has confirmed and justified the use of Tagetes minuta plant leaves amongst the people especially those in rural communities

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P7. HEAVY METAL TOXICITY in THE GEOTHERMAL WATERS

Selma ÖZTEKĠN1*, Esma SÖYLEMEZ1 1Middle Black Sea Passage Generation of Agricultural Research Station Director, Tokat, TÜRKĠYE *[email protected]

The world needs alternative renewable primary energy resources. One of alternative energy sources is geothermal waters. Geothermal waters have been used for multiple purposes such as irrigation, fishing, greenhouse heating, mushroom growing, thermal spring. Geothermal waters are originated from volcanic areas. The hot waters contacting with the rocks absorb many of metal. The absorbed metals in the waters interfere to soil and groundwaters The heavy metals solubled in high concentrated are toxic effect. Boron and arsenic are two metals present the most in the geothermal waters. The quantity of boron and arsenic and derivaties of them in waters became a basic problem in soil and water. The boron in soil changes from 10 to 300 mg/kg depending on amount of organic matter, soil type and precipitation. The boron in groundwater occurs via washing of rocks and soils containing borate and borosilicate. Geothermal hot waters convert arsenic sulfides into arsenic trioxide by weathering of rocks via temperature effect. Therefore, the arsenic compounds mixes into rivers or groundwaters after dissolution. Consequently the groundwater pollution rich arsenic is a serious threat to mankind all over the world. It is reported that the concentrations of arsenic and boron in the groundwaters are 0.1-1.5 mg/l and 1-60 mg/l, respectively. Arsenic causes pollution by leaching of agricultural soils and then mixed with potable waters. WHO reported that the concentrations of arsenic in potable water have to be between 10 and 50 mg/l. The serious healthy problems caused by the arsenic in potable waters have been proved with many researches. The high concentrations of boron in the potable waters cause soil toxicity. Thus, the soil fertility and quality decreases, this affects crop rotation negatively.

The effects of arsenic and boron in the geothermal waters of Turkey on the human health and environment will be discussed in this review paper.

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P8. GRAYANOTOXIN in BREAD: A RARE CASE of MAD HONEY

Bulut DEMĠREL1*, Kenan Can TOK2 1DıĢkapı Yıldırım Beyazıt Training and Research Hospital, TÜRKĠYE 2Ankara University, Institute of Forensic Sciences, Ankara, TÜRKĠYE

Mad honey intoxication occurs with consumption of the honey which contains grayanotoxin produced from Rhododendron flower. The intoxication cases are seen in Turkey especially after consumption of the honey produced in the springs of Black Sea region. Grayanotoxins are nitrogen-free polyhydroxy hydrocarbons and produce parasympathetic effects by binding sodium channels. In our case a 58-year-old male patient admitted to emergency service with loss of consciousness. In his medical history, he hospitalized two weeks ago because of mad honey poisoning. We learned that from his relatives, he used same honey as ingredients when making bread. He responded to treatment and recovered without sequelae. In the literature for the first time we are promoting a mad honey case without direct contact. In conclusion, it is speculated that toxins cannot be destroyed by cooking.

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P9. A DIFFERENT CAUSE OF BURN: THE CEMENT

Bulut DEMĠREL1*, Kenan Can TOK2 1DıĢkapı Yıldırım Beyazıt Training and Research Hospital, TÜRKĠYE 2Ankara University, Institute of Forensic Sciences, Ankara, TÜRKĠYE

Cement is one of the most commonly used substances in the construction industry. Although frequently occurring side effects and burns, there isn‘t enough warning and protection. Cement mainly consists of tricalcium silicate. Heat, calcium ions and hydrogen ions are observed after the interaction of tricalcium silicate and water. Due to excessive release of alkaline hydroxide ions (OH) to environment, pH rapidly rises to over 12. This alkaline medium may cause burns. Alkali burns‘ progress is rapid because of liquefaction necrosis. As well as long-term irrigation, advanced and deep penetrations might need incision.Cement burns in the construction industry poses a threat to employees and are difficult to treat because it is an alkaline burns and can cause cosmetic problems. Informing employees and the preventive measures in construction is required.

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P10. A RARE CASE OF DERMATITIS RELATED TO ST. JOHN'S WORT

Bulut DEMĠREL1*, Kenan Can TOK2 1DıĢkapı Yıldırım Beyazıt Training and Research Hospital, TÜRKĠYE 2Ankara University, Institute of Forensic Sciences, Ankara, TÜRKĠYE

The effects and the adverse effects of alternative medicine products, growing in recent years, are a matter of debate. St. John's Wort is one of the leading plant and product of alternative medicine market in our country and the world. As well as it is consumed by making tea, creams and oils for external use are also available. Despite a detailed examine and well known structure of this plant, we do not know enough detail about the adverse effects of St. John's Wort. In our case, a 47-year-old female patient was admitted to the emergency department with intensive scalp rash and pruritus. As a result of medical history, we learned that the patient used St. John's Wort cream and diagnosed with dermatitis. Patient recovered without sequelae after the necessary treatment.St. John's Wort that contains anthraquinone compounds, flavonoids, tannins, phenols and various essential oils, has been shown antidepressant, antimicrobial and antiviral effects in some studies but available data are insufficient. Extensive control mechanisms must be developed for plants likeSt. John's Wort on market. Clinical studies are needed for investigating the effects of substances to be used as alternative medicine.

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P11. EFFECT MECHANISM AND GENETIC RESISTANCE OF WARFARIN

Bulut DEMĠREL1*, Kenan Can TOK2 1DıĢkapı Yıldırım Beyazıt Training and Research Hospital, TÜRKĠYE 2Ankara University, Institute of Forensic Sciences, Ankara, TÜRKĠYE

The most popular coumarin anticoagulant on the world is warfarin sodium.In 2012, it has been involved in more than 31 million prescriptions in the United States.Warfarin prescriptions increased by 45% between 1998 and 2004and continue to increase. However, warfarin is a one of the risk-forming drugs.Despite the frequent use, an increase in mortality and morbidity is seen because of overuses and adverse effects. Warfarin is the second drug which has most adverse effects after the insulin. Due to improvements in pharmacogenetics, we were learned that two genetic mechanisms neutralize the warfarin.One of these is single nucleotide polymorphisms in VKORC1 and the other is single nucleotide polymorphisms in CYP2C9. Previous studies have determined single nucleotide polymorphisms in different populations and it is mentioned that 68% of patients had genetic sensitivity. The discovery of new polymorphisms owing to developments in pharmacogenetics and becomes to be used routinely these polymorphisms is required to reduce the adverse effects of warfarin.

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P12. A CASE OF DERMATITIS RELATED TO THE MARIGOLD PLANTS

Bulut DEMĠREL1*, Kenan Can TOK2 1DıĢkapı Yıldırım Beyazıt Training and Research Hospital, TÜRKĠYE 2Ankara University, Institute of Forensic Sciences, Ankara, TÜRKĠYE

In our country and the world, alternative medicine is becoming increasingly popular.Some problems are emerging with this orientation which contains mostly herbs and natural minerals.Lack of knowledge of a used plant‘s ingredients and the change of exposure dose aresome of these problems. An active substance which sold on the market without passing the clinical proceduresmay cause more harm than benefit. In our case, 38-year-old woman patient was admitted the emergency department with complaining of rash, itching and burningon her body. There is no previously known disease and allergy in her story.The patient said that she used yellow oil on her skin cracks by given her neighbor. After a half our rash began to occur to her body.We learnt that her neighbor had bought the oil of marigold and given to our patient by his relatives Patient who responds to antihistamines was discharged from follow-up after three hours.

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P13. CLINICAL RESEARCH AND THE CRIME: CASE REPORT I

Arınç KAFTAN, Muğla Sıtkı Koçman University, TÜRKĠYE

Fundamental right to apply the judicial authority on a criminal case is protected under the National Constitution. In this study an unlawful clinical research has been summarized. An organised crime was reported the public prosecutor‘s office by the crime-victim. As concerned by the negative impact of an organized crime on human rights it was declared in the United Nations Congress on Crime Prevention and Criminal Justice in 2010 that a humane criminal justice system is based on the commitment to uphold the protection of human rights and prevention of crime. According to the Directive 2012/29/EU of the European parliament and of the Council establishing minimum standards on the rights, support and protection of crime-victims Council Framework Decision 2001/220/JHA Directive no.9 crime-victim should be protected from revictimization, intimidation and retaliation. The Directive 2012/13/EU of the European Parliament and of the Council on the right to information in criminal proceedings Directive no.21 refers to the meaning of Article 5(1)(c) European Convention of Human Rights on accused persons who are deprived of liberty. The order of a public prosecuter was the sole reason ―crime-victim‖ to be arrested for a clinical research by force. In Article 19 within the National Constitution it‘s regulated that any act against liberty and safety should be facilited under judicial decisions. Above case was not only a reflection of democratic standards not acceptable in domestic law but also a reflection not preventing crime against society.

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P14. MUTAGENIC ACTIVITY OF 4 NEWLY SYNTHESIZED HETEROCYCLIC COMPOUNDS

Fatma ZILIFDAR1*, Egemen FOTO1, Ömür BOSTANCI1, Sibel SARI1, Kayhan BOLELLI2, Ġsmail YALÇIN2, Nuran DIRIL1 1Molecular Biology Department, Faculty of Science, Hacettepe University, Beytepe, Ankara, TÜRKĠYE 2Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ankara University, Tandogan, Ankara, TÜRKĠYE *[email protected]

Heterocyclic compounds, structurally similar to natural biochemical molecules, are usually used for the anticancer drug design. Since they can interact with DNA, they are able to show mutagenic or genotoxic effects. They show their anticancer effects by inhibiting cell proliferation and inducing apoptosis. The first step to select effective compounds is using simple, rapid and inexpensive in vitro tests. Although there are several mutagenicity and genotoxicity tests for this purpose, Ames test is the main mutagenicity test that can be carried out in many laboratories.

In our study, we have evaluated mutagenic activities of 4 new benzothiazole derivatives,which are bicylic heterocyclic compounds. Ames mutagenicity test has been used, based on the method of Maron and Ames. In the experiments, Salmonella typhimurium TA98 strain was used to detect for frameshift mutagens and S. typhimurium TA100 strain was used to detect for base-pair substitution mutagens. In addition, the mutagenic potentials of metabolites of the compounds were evaluated by adding metabolic activation system, S9 mix. All determinations were made in triplicate. Results were evaluated with Student‘s-T test with the confidence interval 95-99%.

According to the results of plate incorporation test, in the absence of the metabolic activation system only 1 numbered compound (50 µg/plate) showed mutagenic effects on S. typhimurium TA98. All of the other tested compounds did not exhibit any mutagenic effects on TA98 and TA100 strains in the presence and absence of S9 mix.

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P15. HEAVY METAL CONTAMINANT IN PHOSPHORUS FERTILIZERS

Selma ÖZTEKIN Middle Black Sea Passage Generation of Agricultural Research Station Director, Tokat, TÜRKĠYE

Phosphorus fertilizers are the most important source of toxic metals in agricultural soils. While heavy metal toxicity in soil occurs via excessive use of phosphorus fertilizers, leads to changes in the soil chemicals properties.The concentrations of heavy meta lin soil can be influenced by many factors, such as climate, parent material and agricultural activities. Heavy metals may be added to soil with chemical and organic fertilizers. Heavy metal toxicity in soil and plant occurs via overuse of chemical and organic fertilizers. Cadmium, arsenic, nicel and lead found in fertilizers applied to agricultural soils. Cadmium concentration passes 3 mg/kg via applied of excessive phosphorus fertilizers in soil. Cadmium is a heavy metal that is easily pass from soil to plant. Cadmium accumulation inedible portions of the plant's is threat to environmental health. Cadmium concentration in soil depend on parent material, organic material, iron, aluminumoxides, agricultural activities such as irrigation or fertilizer use.In addition, crop rotation and tillage have a important impact upon the Cd content of both plant and in soils. Cadmium quantity in agricultural soil increases via unconsciously used of DAP, TSP and compose fertilizers. As, Cd and Pb concentrations in soil were correlated with excessive the use of phosphorus fertilizers. When Cd concentration of soils exceeds 150 ppm, this cadmium creates hazard in both plant and human health. Soiltype, plant uptake and leaching are determined the levels of heavy metals in soil. Heavy metal contamination of the agricultural soils occurs due to long term agricultural activities. Heavy metals combined with organic acids are carry in depth in the soil and may also lead to groundwater and irrigation waters pollution. In this review, the causes of the toxic effects of phosphorus fertilizers in agricultural soils and effects on environment health of phosphorus fertilizers will be discussed.

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P16. MUTAGENIC ACTIVITY OF SOME BENZOTHIAZOLE DERIVATIVES

Egemen FOTO1*, Fatma ZILIFDAR1, Sibel SARI1, Ömür BOSTANCI1, Kayhan BOLELLI2, Ġsmail YALÇIN2, Nuran DIRIL1 1Molecular Biology Department, Faculty of Science, Hacettepe University, Beytepe, Ankara, TÜRKĠYE 2Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ankara University, Tandogan, Ankara, TÜRKĠYE *[email protected]

Design of new anticancer prodrugs is important source to the development of antitumoral agents that can be effective on resistant cancer cell types and have fewer side effects. The first step is to select effective compounds by simple, rapid and inexpensive in vitro tests. Although, there are several mutagenicity and genotoxicity tests for this purpose, Ames test is the main mutagenicity test that can be carried out in many laboratories.

In our study, we have studied 5 new benzothiazole derivatives, which are bicylic heterocyclic compounds. These compounds were taken advantages of some mainful characteristics like showing mutagenic effects, causing aneuploidy in chromosomes, inducing apoptosis and inhibiting cell proliferation. Thanks to their such kinds of features, benzothiazole derivates are used in the synthesis of anticancer drugs. To evaluate mutagenic potentials of compounds Ames mutagenicity test, and plate incorporation assay, have been used based on the method of Maron and Ames. We used salmonella typhimirium TA98 and TA100 strain in the test system. Also metabolic activation system (S9 fractions) was added for the evaluation of mutagenic potential of metabolites of the compounds. All determinations were made in triplicate. Results were evaluated with Student‘s-T test with the confidence interval 95-99%. According to the assay results, in the absence of the metabolic activation system 5 (50 and 75 µg/plate), 6 (50-150 µg/plate) numbered compounds showed mutagenic effects on S. typhimurium TA98 while they have no mutagenic potentials in S. typhimurium TA100 strain. None of the tested compounds showed mutagenic effect in the presence of the metabolic activation system.

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P17. HISTOPATHOLOGICAL STUDIES ON SOME ORGANS OF CYPRINUS CARPIO AND TINCA TINCA FROM MOGAN LAKE

Semra BENZER1*, Ali GÜL1, Belda ERKMAN2 1Gazi Faculty of Education, Gazi University Ankara, TÜRKĠYE 2Faculty of Science, Aksaray University Aksaray, TÜRKĠYE *[email protected]

This study deals with the physicochemical water parameters of Mogan Lake and their histopathologic effects upon Cyprinus carpio and Tinca tinca. This study was carried out on 5 (Cyprinus carpio) and 19 (Tinca tinca) caught in Mogan Lake in 2013. The fork lenght and weight were calculated as 250-330 mm, 274.25-761.76 g and 230-295 mm, 222.80-447.42 g for Cyprinus carpio and Tinca tinca respectively. The changes of the fish tissues were determined by the use of routine histological methods. There were bronchitis, telangiectasia and passive hyperemia determined in gills; hydropic and vacuolar degeneration were seen in livers; there were hyperemia in kidney tissue. Bronchitis and hyperemia were intensively observed in Cyprinus carpio and Tinca tinca. Focal hepatitis was much more intensive in Cyprinus carpio.

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P18. BIOACUMULATION OF ARSENIC AND BORON IN WATER, SEDIMENTS AND TISUES OF FISHES FROM EMET STREAM (TURKEY)

Semra BENZER Gazi Faculty of Education, Gazi University Ankara, TÜRKĠYE [email protected]

In this study, the concentrations of arsenic and boron were determined in the water and the sediment, as well as in the muscle tissues of Leuciscus cephalus, Alburnoides bipunctatus, Barbus plebejus and Capoeta tinca from Emet Stream. The fish samples were caught in May 2011 and September 2012. The metal concentrations in the water samples were as follows: in Hisarcık, arsenic was 342.1-1002 µg l-1, and boron was 4697-14490 µg l-1; and in Etibor, arsenic was 137.1-924.5 µg l-1, and boron was 2421-14900 µg l-1. The metal concentrations in the sediment samples were as follows: in Hisarcık, arsenic was 920 - 925 mg kg-1, and boron was 300 - 310 mg kg-1; and in Etibor, arsenic was 14.51-3317.1 mg kg-1, and boron was 14.22-1014.01 mg kg-1. The mean tissue concentration of arsenic was lower than the TFC and WHO limits. Boron has been identified in fish tissues at concentrations between 0.26 and 2.96 mg kg-1. The bioacumulation in the muscle tissues of all fish species caught from Emet Stream did not exceed the limit values.

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P19. DEATH DUE TO HIGH DOSE COLCHICINE INTAKE

Afsin Emre KAYIPMAZ1*, Hasan ORGEN2, Tufan Akin GIRAY1, Cemil KAVALCI1 1Department of Emergency, Baskent University Faculty of Medicine, Ankara, TÜRKĠYE 2Department of Anesthesiology and Reanimation, Anadolu Hospital, Sivas, TÜRKĠYE

Colchicine is an antiinflammatory agent used for the treatment of Behçet‘s Disease, Familial Mediterranean Fever, and gout. This study presented a colchicine-induced fatality case in an attempt to draw clinicians' attention to suicide risk in patients using colchicine. A 19-year-old woman presented to our emergency department after taking 200 colchicine tablets 0.5 mg for suicidal purpose 24 hours ago. She had Behçet‘s disease for which she had been using colchine 0.5 tid. Her admission vital signs were as follows: Body temperature 36.3°C, blood pressure 60/40

mmHg, heart rate 107 bpm, SpO2: 97%, and respiratory rate 22/min. Her general appearance was moderately disstressed and she was conscious but somnolent. Her Glasgow Coma Score was 13. Physical examination revealed bilaterally positive light reflexes and active deep tendon reflexes. She was transferred to intensive care unit. At the third day of admission she developed sudden-onset loss of consciousness and respiratory failure. Her GCS point dropped to 3. She was intubated and connected to mechanical ventilator. There was not any pathology or intracranial hemorragia on CT. She was begun on total parenteral nutrition and dopamin and noradrenaline infusion. Despite having leukocytosis (40900) at admission, she developed pancytopenia (Hemoglobin: 11 g/dl , Platelets: 39000, Leukocytes: 3890) 4 days after oral intake. Five units of thrombocyte suspensions were administered. She later developed liver and renal functional abnormalities (AST: 2153, ALT: 656, : 175, Creatinine: 1.54). She was received supportive therapy for multiorgan failure. She developed cardiopulmonary arrest at 4th day and died after failed CPR attempt.

An oral colchichine intake of 0.5-0.8 mg/kg is toxic and associated with high mortality. It has been reported that an intake above 0.8 mg/kg has a fatal course (1-3). Our patient had a body weight of 50 kg and the dose of her colchichine intake corresponded to 2 mg/kg. The patient died at the 4th day of admission owing to high dose colchichine intake.

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P20. SYSTEMIC TOXICITY of A LOCAL ANESTHETIC AGENT in EMERGENCY DEPARTMENT

Afsin Emre KAYIPMAZ*, Tufan Akin GIRAY, Cemil KAVALCI, Murat MURATOGLU, Suleyman Serdar TASCI Department of Emergency, Baskent University, Faculty of Medicine, Ankara, TÜRKĠYE

Lidocaine has been reported to cause central nervous system side effects including numbness around mouth, dizziness, ataxia, agitation, seizure, coma, and respiratory failure in the course of systemic toxicity after high-dose use. In this case report we present a case of lidocaine toxicity after high-dose application of this drug in complementary medicine setting.

A 62-year-old woman presented to our emergency department with altered consciousness and seizure activity. Her admission GCS was 9. Her past history was notable for application of paravertebral ozone therapy and intramuscular lidocaine 200 mg for muscle spasm in a private clinic some hours ago at the same day. She was deteriorated a few minutes after lidocaine administration, with altered consciousness and generalized seizure-like contractions. She vomited once at initial admission to emergency department. Her vital signs were as follows:

Body temperature 36°C, respiratory rate 22/min, BP 130/79 mmHg, SpO2 100%, and heart rate 62 bpm. ECG showed normal sinus rhythm. Her past history was notable for Hashimoto thyroiditis-induced hypothyroidism and hypertension. Head and thoracic CT with contrast, obtained for possible cerebral and pulmonary vascular events, revealed no pathologies. The patient was admitted to the intensive care unit and brain diffusion tests and diffusion MRI were performed, both revealing no pathology. An EEG examination showed no epileptiform activity. The patient experienced no additional symptoms during hospitalization and was discharged at 3rd day on levetiracetam 2x500 mg.

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P21. NEW GENERATION OF NON-TOXIC SYNTHETIC POLYMERS

E. ALTAY OZTURK1*, F. OZTURK2, M. ALTIKOĞLU3, T. EREN3 1Gazi University, Graduate School of Natural and Applied Sciences, Ankara, TÜRKĠYE 2Ankara University, Institute Of Forensic Sciences, Ankara, TÜRKĠYE 3Department of Chemistry, Yildiz Technical University, Esenler, Istanbul, TÜRKĠYE *[email protected]

Bacteria are an important part in our daily lives. The common objects such as public telephones, children toys, pen are not antibacterial and they require modification. Twelve million deaths occur in the world annually and add millions dollars to healthcare costs due to infection, clearly this war against bacteria is a significant problem. Hospitals are the main source and origin of multiple resistance bacteria. Patients infected with these clinical courses require prolonged hospital treatments. Pathogenic bacteria can easily deposited on the hospital objects such as linen, sickbed, used glove, faucet, floor, walls etc. When these surfaces are touched by infected people, then bacterial infections can be transferred. This is one of the primary pathways for the acquisition of nocosomial infectious pathogens. Coating of these types of material surfaces with biocides is one of the valuable applications for the activity against to bacteria.

Nowadays, due to the increase of bacteria resistance, activity of antibiotics has led to decrease. So, high efficiency, preferably selective and low toxicity, need to focus on the synthesis of new antibacterial agents is an issue. Antibacterial agents not only about drug, in material of textile, prosthese, catheter tube, wall paint, water treatment plants and food packaging must review a wide range, before the life don't contaminate with bacteria, must kill it on ―fomit‖.This situation provides extremely advantage to us.

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P22. EVALUATION OF DNA DAMAGING POTENTIALS OF LUMINOL, HEMASCEIN AND BLUESTAR USING THE COMET ASSAY

Melika BEKTAġ1, Tolga ÇAVAġ2, Belgin ĠZGĠ1,3 1Uludag University, Graduate School of Natural and Applied Science, Department of Criminalistic, Bursa, TÜRKĠYE 2Uludag Univesity, Science and Art Faculty, Department of Biology, Bursa, TÜRKĠYE 3Uludag Univesity, Science and Art Faculty, Department of Chemistry, Bursa, TÜRKĠYE

One of the most important problems in the field of forensic sciences is the perfectly protection of DNA in order to obtain suitable DNA fingerprints from biological samples. Therefore it is critically important to minimize the effects of physical and chemical factors which could cause DNA degradation during sampling processes.

The regants such as Luminol, Hemascein and BlueStar are used to determine the presence of blood. The heme-group of hemoglobine acts as a catalyst and reacts with hhdrogen peroxide to produce blue light. The single-cell gel electophoresis (SCGE), also known as the Comet Assay, is a sensitive and simple technique used to measure deoxyribonucleic acid (DNA) strands breaks in eukaryotic cells. Electrophoresis of lysed cells results in comet-like images, observed and scored under fluorescene microscope.

In this study, the DNA damaging effects of Luminol, Hemascein and Bluestar were evaluated on human blood samples using the Comet Assay.

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P23. EXPERT, CLINICAL EXPERT AND THE CRIME: CASE PRESENTATION

Arınç KAFTAN Muğla S.K. University, TÜRKĠYE

Expertise report as a legal tool has been used to discuss the proof where government institutions may contribute on behalf of the legal entity. In this study the share of duty between criminal expert and the clinical expert in a criminal proceeding has been discussed. In the concrete situation a legal procedure was conducted by using an unreal private document. Whenever the claim was brought before the local authority the unreal private document was submitted to one of the national criminal expert institution for investigation. An expertise report was returned that the document for investigation has not undergone any criminal investigation at all. The expertise report resulted with accusing of the crime victim and it has been moved to the clinical research step with the order of the court in a criminal cause thereafter. There was no criminal investigation of the crime no right to attend other proceedings and no satisfaction for the crime victim which is undoubtely the desire of anyone who has been injured by another. In sum, the victims‘ right as a mode of public social welfare was excluded from the legal response of the criminal justice to the party indeed.

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P24. THE RECOVERY EFFECTS of OLIVE LEAF EXTRACTS on MERCURY EXPOSURE in SOME BIOCHEMICAL PARAMETERS of NIL FISH (OREOCHROMIS NILOTICUS L. 1758)

Hikmet Y. ÇOĞUN1*, Özgür FIRAT2, Özge FIRAT2, Gülbin GÖK3, Tüzin AYTEKĠN YÜZEREROĞLU4, Özge TEMĠZ4, Ferit KARGIN4 1Department of Physiology, Ceyhan Veterinary Faculty, Cukurova University, 1330 Adana, TÜRKĠYE 2Department of Biology, Faculty of Science and Letters, Adiyaman University, 02040 Adiyaman, TÜRKĠYE 3Research Lab. Gazi University, GölbaĢı, Ankara, TÜRKĠYE 4Department of Biology, Faculty of Science and Letters, Cukurova University, 01330 Adana, TÜRKĠYE *[email protected]

In this study was to describe the effect of olive leaf extracts, oleuropein (OE), compound in blood biochemical parameters (ALT, AST and Glucose) on acute mercury (Hg) exposure in Nil fish Oreochromis niloticus for 4 days. Fish were exposed to 0.01 mg/L Hg and 0.01 mg/L Hg + 0.1 mg/L OE for 4 days. Biochemical parameters of fish blood were determined by spectrophotometric method. The exposure of O. niloticus to Hg alone resulted in decreases in biochemical (ALT, AST and Glucose) activity. OE, in combination with Hg, partially or totally caused alleviation for the toxic effect of Hg on biochemical parameters. The results of our study showed that OE has a protective effect against toxicity induced by Hg. All biochemical parameters were found to be statistically significant (p<0.05) in Hg+OE concentrations.

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P25. ANTICOAGULANT RODENTICIDE POISONING IN PREGNANCY

Zeynep ÖZTÜRK1*, Serap ÇUHADAR2 1 Ġzmir Atatürk Training and Research Hospital, Department of Clinical Pharmacology and Toxicology, Ġzmir, TÜRKĠYE 2 Ġzmir Atatürk Training and Research Hospital, Department of Medical Biochemistry, Ġzmir, TÜRKĠYE

Rodenticides are the most commonly used toxic agents for the suicide attempts because of their ready availability. Most of them are warfarin-type anticoagulants and the long-acting anticoagulant products (e.g., brodifacoum, bromadiolone, etc.) known as ―second generation‖ or ―superwarfarins‖. For humans, even a single dose of these agents can be lethal. The purpose of this report is to increase the awareness of rodenticide poisoning and suicide attempts.

A 24-year-old multiparous and 11 weeks pregnant woman attempted suicide by taking brodifacoum as rodenticide. On arrival in the emergency department, she had no sign of hemorrhage, but nonspecific complaints such as nausea, numbness and feeling unwell. According to her medical history, she had taken psychotropic medication, but discontinued abruptly because of the pregnancy. Laboratory test results included hyponatremia, hypocalcemia, slightly lower blood urea nitrogen (BUN), creatinine levels and shortened activated partial thromboplastin time (APTT). The patient was monitored for 72 hours and discharged home after normal laboratory test results of renal functions, electrolytes and APTT. A few days after, she consulted to Clinical Pharmacology and Toxicology Counselling Service for toxicity risk assessment. The information about the teratogenic risks of the agent was provided and was followed till delivery. No sign of perinatal complications was noticed.

Superwarfarins are long-acting anticoagulants that may cause bleeding, internal hemorrhage and prolonged blood clotting times (PT, APTT). In this case, the shortened APTT might be due to stress and pregnancy. In conclusion, this clinical presentation can be defined as a simulation or atypical intoxication.

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P26. GENE POLYMORPHISMS INFLUENCING RESPONSE TO LEAD EXPOSURE

Kaan SAVAġOĞLU1, Zeynep ÖZTÜRK2* 1 Ġzmir Atatürk Training and Research Hospital, Department of Medical Genetics, Ġzmir, TÜRKĠYE 2 Ġzmir Atatürk Training and Research Hospital, Department of Clinical Pharmacology and Toxicology, Ġzmir, TÜRKĠYE

Lead is an element that has been used by mankind for 6000 years due to its specifications like softness, high malleability, ductility, low melting temperature and corrosion resistance. Lead is the second most dangerous element coming after arsenic and its toxic effects on human are due to causing dysfunction of various organs such as kidney, bones, hematogenesis, cardiovascular system, nervous system.

Several studies have shown that genetic factors can influence toxicity in lead exposed individuals. Aminolevulinic acid receptor (ALAD), hemochromatosis gene (HFE), vitamin D receptor (VDR), glutathione S transferases (GST), metallothioneins (MT), XRCC3-241C/T genes are candidate genes for regulation of lead toxicity. Individuals with GSTM1, GSTT1 and GSTP1-Val105 of GST genes have been shown to be more sensitive to lead exposure. Low blood lead levels were detected in individuals with ALAD2 allele of ALAD G177C polymorphism (rs1800435), H63D and C282Y wild types of the HFE gene, the VDR BSM1 allele b, MT1 1245 A/G (rs8052394) polymorphism of MT gene. In contrast, higher mean blood lead levels were determined for individuals with GG genotype in MT2A 5A/G (rs28366003) and with T allele in the XRCC3-241 C/T polymorphisms.

In our country, identification of existing of environmental risks and determining genetic predispositions represent its importance in terms of public health in order to reduce toxicity resulting from lead exposure. Multidisciplinary studies conducted on this topic will provide very important data for government agencies and scientists

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P27. DEVELOPMENTAL TOXICITY AND DRUG RISK ASSESSMENT IN PREGNANCY

Zeynep ÖZTÜRK Ġzmir Atatürk Training and Research Hospital, Department of Clinical Pharmacology and Toxicology, Ġzmir, TÜRKĠYE

Drug use during pregnancy can prove teratogenicity and cause a permanent abnormality of structure or function on fetus. The risks for the fetus are various, with the most serious being congenital defects, growth impairment, fetotoxic effects and fetal death. However, it does not mean that exposure to a drug will always cause harm. Teratogenic effects of drugs depend on dosage, gestational and administration timing.

Teratogens are agents that can induce developmental toxicity or increase the incidence of a congenital malformation. Major congenital defects occur in 1-3% of the general population at birth. Approximately 2-3% of birth defects are associated with drug exposure. The remaining defects are caused by other environmental exposures during pregnancy such as infection, maternal disease states and ionizing radiation. The FDA (Food and Drug Administration) pregnancy risk classification is a rating system to categorize the potential fetal risks due to drugs. Although it provides short and practical information, it is inadequate if used as the sole resource. Labeling for pregnancy generally can not address the spesific clinical circumstances for which the drug is being used. Moreover, the use of the wording ―high risk‖ or ―contraindication‖ might result in unnecessary termination of pregnancy.

Patients exposed to drugs and known teratogens during pregnancy should be informed of the potential side effects. A detailed maternal medical history can help to avoid unnecessary diagnostic intervention. It is also important to contact pharmacology consulting services for more information relating to chemical exposure and medication.

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P28. DRUG INDUCED LIVER INJURY AND BIOMARKERS USED FOR ITS DETERMINATION

Hatice Gül GÖKTAġ1,2,*, Merve BACANLI1, NurĢen BAġARAN1 1Hacettepe University, Faculty of Pharmacy, Department of Toxicology, Ankara, TÜRKĠYE 2Çukurova University, Faculty of Pharmacy, Department of Toxicology, Adana, TÜRKĠYE

Liver is primarytarget organ fordrugtoxicity since it is major organ responsible for the metabolism and detoxifiction of xenobiotics. Drug induced liver injury (DILI) is a clinical condition that defines liver damage due to drugs, herbal products and food supplements. DILI can cause severe liver damage which may progress to acute liver failure and ultimately can cause serious morbidity and mortality. DILI occurs directly or by idiosyncratic mechanisms. It is a significant impediment to the development of new therapies as the biggest reason for the removal of a drug from the market or assignment black box warning to some drugs. In order to reduce the risk of DILI, it is important to be careful in the prescribtion of drugs in elderly people and patients having polypharmacy and chronic diseases. Hepatotoxicity can be determined by measuring the serum enzyme activities such as alkaline phosphatase, aspartate amino transferase, alanine amino transferase and determination of total bilirubin concentration. However these biomarkers are not sufficient for the sensitive and specific determination of DILI. More importantly, these biomarkers indicate the present damage and don‘t inform the future damage. Therefore, it is necessary to develop new biomarkers. Nowadays, molecular proteins such as keratin-18, cytochromec, glutamatedehydrogenase, high mobility group box-1proteins, malatedehydrogenase, purinnucleosidephosphorylase, sorbitoldehydrogenase and microRNAs are the most commonly recommended biomarkers. Using new biomarkers as a complement to classic biomarkers will contribute a lot to diagnosis and treatment of DILI.

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P29. PHOTOCATALYTIC REMOVAL OF TOXIC CR(VI) WITH PHYTALLOCYANINE IMMOBILIZED TIO2

Melek KOÇ, Cansu ALBAY, Ġlknur ALTIN, Ġsmail DEĞIRMENCI, Rıza BAYRAK, Münevver SÖKMEN Department of Chemistry, ScienceFaculty, Karadeniz Technical University, 61080, Trabzon, TÜRKĠYE

Chromium is one of the metal pollutants which is used in different industrial fields. Because of its toxicity and mobility hexavalent chromium Cr(VI) is trouble matter and remove it from the waste waters is quitediffucult. Cr(VI) exposure via inhalation cause carcinogenic effect on the living mechanism. As Cr(VI), a potential carcinogen present in the environment, represents a significant safety concern, it is currently the subject of an EPA health risk assessment. Therefore, sensitive and selective removal of this specie is highly desired. Removal of Cr(VI) in waste waters have been improved physical, chemical, biological procedures and so forth. In recent years, photocatalytic reduction as advanced chemical techniques is a suitable way for effective removal of Cr(VI). This study have been focused on

photo reduction of Cr(VI) with sensitized TiO2 under UV-vis light. In this study, phthalocyanine (Pc) compounds are used as dye sensitizer. Pc molecules are also known to have reductive properties and removing it from the aqueous solution after treatment is

difficult so they are stabilized on to TiO2 support surface.For this, 1%(w/w) Pc (two different

chemical structures) was immobilized on TiO2. Pc/TiO2 derivatives (2g/L) were used for photocatalytic reduction of 10 ppm Cr(VI) as model pollutant.In this process, Cr(VI) solution was exposured with UV source (λ=365 nm) for 150 minutes.After a certain illumination period remaining unreduced Cr(VI) concentration was measured by spectrophotometric method. Control experiments were carried out with neat Pc and the results were compared

with Pc-TiO2.

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P30. EFFECTS OF TOXIC METALS ON GLUTATHIONE S-TRANSFERASE ACTIVITIES, GLUTATHIONE AND PROTEIN LEVELS IN SELECTED WHEAT VARIETIES

Ceyhan HACIOĞLU Anadolu University, Graduate School of Sciences, EskiĢehir, TÜRKĠYE

Heavy metals (HMs) cause oxidative damage in plants through reactive oxygen species (ROS) formation. However, cells can detoxify the harmful effects of ROS with the help of enzymatic or nonenzymatic antioxidant defense mechanisms. Activation and induction of glutathione S-transferases (GST) enzymes are one of the metal detoxification mechanisms in plants. Glutathione S-transferases (GST) are a diverse group of enzymes catalyzing the conjugation of electrophilic xenobiotic substrates with the tripeptide glutathione (GSH). GSH is considered as one of the most important metabolite for intracellular defense against ROS induced oxidative damage. In this study, the effects of different concentrations of CdCl2 and PbCl2 treatments on contents of GSH, protein and GST activities in the roots and shoots of Triticum aestivum L. cv. Ġzgi-2001 and Alpu-2001 were detected in hydroponic solutions. The application of HMs to plants caused differences in protein contents by comparing to their control groups. While the increase in shoots was higher than in the roots of Ġzgi-2001, protein contents decreased more in roots of Alpu-2001. In GSH concentration measurements, the shoots of Alpu-2001 have shown higher than in the shoots of Ġzgi-2001. The application of HMs to plants was caused a similar increase in GST activities by comparing to their control groups. The variable results which observed in protein contents, GSH contents and GST activities are reflecting a difference in the rate of metabolism with regard to HMs between varieties.

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P31. AGE- AND SEX- RELATED RISK FACTORS FOR ELEVATED SERUM DIGOXIN LEVELS: A CROSS- SECTIONAL STUDY

Zeynep ÖZTÜRK1*, Serap ÇUHADAR2 1 Ġzmir Atatürk Training and Research Hospital, Department of Clinical Pharmacology and Toxicology, Ġzmir, TÜRKĠYE 2 Ġzmir Atatürk Training and Research Hospital, Department of Medical Biochemistry, Ġzmir, TÜRKĠYE

Digoxin is widely used in controlling ventricular rhythm in atrial fibrillation and in heart failure which cannot be controlled by other medications. Therapeutic levels of digoxin are 0.5- 2 ng/ml. Intoxication may occur after acute accidental or suicidal ingestion or with chronic therapy.

In this study, we aimed to find out the frequency of elevated serum digoxin levels and its association with factors of age, gender and patients‘ health status. A one-year (January- December 2009) cross-sectional study was performed. In total, 741 patients were included in the study. The mean (range) age was 70 (min.17, max.95) years and 565 of 741 patients were elderly (age≥65). The frequency of elevated serum digoxin levels was found to be 14.1% in our study population (n=103). Most of these patients were elderly (93%) and 77% of them were female. The most common diseases and symptoms in patients who had serum digoxin levels greater than 2 ng/ml were cardiovascular (atherosclerotic vascular disease, heart failure, tachycardia, bradycardia), respiratory (dyspnea, respiratory failure), urinary system and cerebrovascular diseases.

This study shows that higher serum digoxin levels are associated with older age and female gender. Increased awareness of medication safety in the elderly is important. Because the volume of distribution and renal clearance of digoxin decline with age, therapeutic monitoring is needed. Additional drugs could also increase digoxin levels and produce toxicity in elderly patients who use multiple medications concurrently. Health professionals should be more aware of these potential drug interactions, and further studies are needed on this topic.

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P32. DIGOXIN TOXICITY AND RENAL FUNCTIONS

Serap ÇUHADAR1, Zeynep ÖZTÜRK2* 1 Ġzmir Atatürk Training and Research Hospital, Department of Medical Biochemistry, Ġzmir, TÜRKĠYE 2 Ġzmir Atatürk Training and Research Hospital, Department of Clinical Pharmacology and Toxicology, Ġzmir, TÜRKĠYE

Digoxin is a cardiac glycoside used to treat congestive heart failure and to slow the heart rate in patients with atrial fibrillation. Because its therapeutic effect works only within narrow window (0.5- 2.0 ng/ml), overdose occurs commonly. Therefore it is recommended to keep the upper value as 0.9 mg/dl and check regularly.

Digoxin toxicity can be caused by high dose levels. Besides low levels of potassium and magnesium is a risk factor although blood digoxin levels are in the therapeutic range. Another problem is the kidney originated digitalis accumulation in the blood.

In this study, the kidney function tests were retrospectively checked in 184 patients (98 female aged 76±9, 86 male aged 73±12 years) treated with digoxin intoxication whose blood levels were detected as >2 ng/ml. All were segregated into two groups [A(n=101), B(n=83)] based on serum creatinine levels (lower than 1.4 mg/dl and higher than 1.4 mg/dl, respectively).

In group B, digoxin and BUN correlated significantly (r=0.322, p=0.003). No significant difference was observed between digoxin levels among groups, but as expected BUN and potassium levels were different. In all, 44% of female, 46% of male patients were suffering from kidney dysfunction. A total of 14% patients were hyperkalemic (>5.5 mmol/l) and 7% were hypokalemic.

As a result, nearly half of the patients with digoxin toxicity were found as suffering from renal function reduction. Especially in the elderly patient group, digoxin blood levels have to be checked regularly and frequently.

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P33. PARACETAMOL AND NAPQI IN BIOLOGICAL FLUIDS, (BLOOD AND URINE) BY USING HPLC AND LC-MS

Pinar TARGAN1, Joshua BOATENG1 1University of Greenwich, Department of Pharmaceutical, Chemical and Environmental Sciences, Faculty of Engineering and Science, Medway, UK

Paracetamol is an acylated aromatic amide, which was firstly introduced into medicine as an antipyretic/analgesic by Von Mering in 1893 and ever since it has been used as a painkiller for home medication and reported as an effective treatment for the relief of pain and fever in adults and also in children. With this degree of success and universal availability it was inevitable that paracetamol would be used increasingly for the fashionable habit of self- poisoning.The major aim of this project was to determine the toxic metabolite of the paracetamol (acetaminophen) in serum (blood) and urine samples for the investigation of accidental drug overdose suicide cases. A human volunteer was made to swallow normal paracetamol dose. Blood samples were taken from a human subject at set time intervalsby trained qualified personnel and centrifuged to obtain serum. In addition, urine samples were collectedat given time intervals from the same individual. Calibration curves for paracetamol and its toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI) were obtained using HPLC and LC-MS. The serum and cleaned urine samples were analysed by HPLC and LC-MS.The

assay was performed by using C18 column and mobile phase of acetic acid and acetonitrile (85:15; v/v). Linearity of the method was assayed in the range of 1.25-100ug/ml for paracetamol and 0.75-50ug/ml for NAPQI, with correlation coefficient of r2=0.9999 for paracetamol and 0.9995 for NAPQI. Paracetamol and its toxic metabolite NAPQI compound were not easy to detectable in shorter times after ingesting the tablet. The compound and its metabolites can be detectable after 24hours due to conjugation in liver and excretion in kidney.

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P34. A SYSTEMATIC REVIEW of CASES in TURKEY OVER THE PAST DECADE

SEZIGEN S1*, EYISON RK 1, KENAR L1 1GMMA, Dept. Of Medical CBRN Defense, Ankara, TÜRKĠYE

We reviewed systematically the national literature which was belonged to the last decade by accessing the MEDLINE database. Pesticide poisoning is a major public health problem in developing countries. The World Health Organization recognizes pesticide poisoning to be the single most important means of suicide worldwide. Suicide is the most common manner of death in pesticide poisonings followed by accidents and homicide.

In 2011, 26.770 tons of pesticides were sold in Turkey. Various outcomes had been reported in different sociocultural regions of Turkey as it is a rare cause of poisoning in the emergency departments. For this reason the magnitude and the national distribution of pesticide poisoning are still unknown.

The most three frequent causes of poisonings were drugs, pesticides, and carbon monoxide respectively. Organophosphate insecticides are the second main group causing poisoning and consequently death after endosulfan. The most common pesticides detected in this group are dichlorvos followed by chlorpyrivos and methyl parathion. Suicidal poisonings are higher than accidental poisonings. Suicides are occurred mostly at home and all accidental poisoning deaths occur in agricultural area. Poisoning incident is observed in youths and females. Oral route is the most preferred method. The number of poisoning cases in summers which reaches a peak in June is significantly higher than cases in winters.

It is suggested that many pesticide-related deaths might be prevented if their use was restricted with new regulations and a specific surveillance system could be maintained.

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P35. COMPARISON OF THE TOXIC POTENCY OF G AGENTS AND VX IN ORDER TO DETERMINE THE FATALITY ESTIMATION AFTER A TERRORIST ATTACK

SEZIGEN S1*, EYISON RK 1 1GMMA, Dept. of Medical CBRN Defense, Ankara, TÜRKĠYE

G agents (tabun, sarin, soman) and Vx which are known as nerve agents have been used both for various military and terrorist purposes at chemical attacks since the First World War. Sarin was used in Syria on August 21, 2013 and it was estimated that death toll ranged from at least 281 to 1.729 fatalities.

The effect mechanism of nerve agents is the blockage of acetylcholinesterase at the neuromuscular junction. Accumulated acetylcholine that cannot be hydrolyzed in the synaptic gap due to inhibition of the enzyme overstimulates the postsynaptic acetylcholine receptors and clinical manifestations are observed in almost all systems including nervous system, eye, respiratory system, cardiovascular system, and digestive system. Paralyzed respiratory muscles cause to death and time of death depends on the concentration of the agent and the exposure time.

Clinical studies showed that average lethal dose for a 75 kg weighted standard man who breathed 15 liters air per minute was 10 mg.min/m3 for Vx, 35-50 mg. min/m3 for soman, 75- 100 mg. min/m3 for sarin, and 150-400 mg. min/m3 for tabun. As the inlet passage of nerve agent vapors to the organism is via airway, LCt50, ICt50, and MCt50 which express vapor toxicity are used in order to compare G agents and Vx.

We aimed to discuss and compare nerve agents comprehensively in mean of toxic potency as the extent of vulnerability to future chemical terrorist attacks varies because of new chemical weapons arsenal of non-state terrorist organizations in Middle East.

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P36. POSTMORTEM EXAMINATION SAFETY REGULATIONS IN PATIENTS WITH SUSPECTED VIRAL HEMORRHAGIC FEVERS

SEZIGEN S1 1GMMA, Dept. of Medical CBRN Defense, Ankara, TÜRKĠYE

Viral hemorrhagic fevers (VHFs) are a group of RNA virus family illnesses including Crimean-Congo hemorrhagic fever (CCHF) and Ebola virus disease (EVD). As VHFs are spreading via biological fluids of infected people, health-care workers are infected while treating patients with suspected or confirmed VHFs because basic hand hygiene, respiratory hygiene, use of personal protective equipment (PPE), and safe injection practices are not strictly practiced. An essential component of control during outbreaks of VHFs is investigation of the causes of recent unexplained deaths with postmortem examination as it is particularly important during the earliest part of the epidemic in order to identify both individuals who have died of VHFs and their contacts.

Medical personnel including coroners, medical examiners, and pathologists should be able to use PPE while performing postmortem examinations. Using appropriate PPE/communication equipment during examination and monitoring the environment could control such stresses that mentioned above.

Physical and physiological impairments that PPE cause distorted vision, limited view, limited hearing and communication, limited touch and tactility, limited movement ability/body functions, limited working time because of limited life of CBRN protective respirator canisters. The effects of these impairments could affect both the survival of the operator in mean of contamination and the likelihood of the medical examination success and this deficiency could cause misdiagnosis which follows malpractice.

This vital handicap could be eliminated by meeting the criteria of PPE which is suitable for the task requirement, training, and fitness requirements by forensic examination teams in a realistic manner.

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P37. CANNABIS USE IN ADOLESCENCE AND SCHIZOPHRENIA

Esra ENGÜR*, Selda MERCAN, Münevver AÇIKKOL Istanbul University, Institute of Forensic Sciences, Forensic Toxicology Laboratory, 34303, Cerrahpasa, Istanbul, TÜRKĠYE *[email protected]

Marijuana is one of the most commonly used illicit drugs. Although cannabis is also considered to be a safe drug, their long-term use causes harmful results. Diagnosis of schizophrenia in older age was found to be associated with consistently cannabis use. Schizophrenia which is characterized by the lack of perception or expression of reality is a common psychiatric disorder. Dependence in adolescence is particularly risky, and this has been proven in both epidemiological and animal studies.

Cannabis intoxication is considered to cause psychotic episode. It is not clear that cannabis use is an enough risk factor and it is not all schizophrenics have used cannabis. However, exposure and the age at first use of cannabis increases the harmful effects and this has been proven in psychosis studies.

First cannabis use in adolescence was associated with an increase risk for psychotic symptoms in adulthood and in Western and non-Western societies have a lot of studies on this issue.

Several studies have shown that, cannabis use carries higher risk since the brain is still developing at the beginning of adolescence.

Although, studies about cannabis use in adolescence as a result of psychotic disorders are still at early stages, it is an issue that should be considered for long term evaluation and schizophrenia in older ages.

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P38. THE HIDDEN DANGERS OF TECHNOLOGY: TOXIC SUBSTANCES IN ELECTRONIC WASTE

Nesrin ĠÇLĠ Ministry of Customs and Trade, Ankara Laboratory Directorate, Kazan, Ankara, TÜRKĠYE

Electronic waste, also recognized as E-Waste, is a combination of used or unwanted electronic products that have exceeded their shelf life. Computer equipment, monitors/TV‘s, cell phones, batteries, stereos, etc. are popular examples of items that contain harmful toxic components that need to be recycled properly. E-waste is currently the largest growing waste stream. It is hazardous, complex and expensive to treat in an environmentally sound manner, and there is a general lack of legislation or enforcement surrounding it.

Today, most e-waste is being discarded in the general waste stream. The composition of e- waste is very diverse and differs across product lines and categories. Overall, it contains more than 1000 different substances which fall into ―hazardous‖ and ―non-hazardous‖ categories; significantly, the toxicity of many of the chemicals in e-waste is unknown. Electronic products often contain several persistent, bioaccumulative and toxic substances including heavy metals such as lead, nickel, chromium and mercury, and persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) and brominated flame retardants.

There are three main groups of substances that may be released during recycling and material recovery, and which are of concern: original constituents of equipment, such as lead and mercury; substances that may be added during some recovery processes, such as cyanide; and substances that may be formed by recycling processes, such as dioxins.

This presentation explores the sources and flows of e-waste, the risks it poses to e-waste workers and the environment, occupational safety and health issues and regulatory frameworks.

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P39. WE ARE NOT AWARE OF THE DANGER THAT WE HOLD IN OUR HANDS: BPA IN THERMAL PAPER

Nesrin ĠÇLĠ Ministry of Customs and Trade, Ankara Laboratory Directorate, Kazan, Ankara, TÜRKĠYE

Bisphenol A (BPA) is a monomer used in manufacturing most polycarbonate plastics, the majority of epoxy resins, and other chemical products. It is also used in a variety of consumer products, including some paper products, particularly thermal receipt papers, for which it is used as a color developer. There is a potential for occupational exposures during thermal paper manufacturing and product end-of-life (i.e., recycling, landfilling, or incineration). Additionally, there may be exposures to workers and consumers while thermal paper is being used and to the general population and the environment from releases during product manufacturing, use, and end-of-life.

Releases of free BPA monomers in thermal paper can occur upon contact with the paper and can be subsequently absorbed into the skin, leading to exposure during handling and use. Because BPA mimics the biological activity of estrogen, many scientists worry that the chemical might induce harm by disturbing hormone signaling in exposed individuals. Chlorinated BPA byproducts may be formed in secondary paper mills that use recycled thermal paper with BPA. Estrogenic activities of chlorinated derivatives of BPA were found to be relatively more potent than BPA. Most alternatives of BPA in thermal paper have Moderate or High hazard designations for human health or aquatic toxicity.

In Europe many countries have banned use of BPA in baby products such as baby bottles. Many companies have voluntarily decided to stop using BPA in their products. However, worldwide use of BPA in thermal paper is not restricted.

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P40. HPLC-FLD METHOD VALIDATION FOR DETERMINATION OF POLYCYCLIC AROMATIC HYDROCARBONS METABOLITES IN URINE

Nesrin ĠÇLĠ1*, Zeliha KAYAALTI2 1Ministry of Customs and Trade, Ankara Laboratory Directorate, Kazan, Ankara, TÜRKĠYE 2Ankara University, Institute of Forensic Sciences, Cebeci, Ankara, TÜRKĠYE

PAHs are because of inducing chromosomal effects in individuals exposed to PAHs, genotoxic carcinogens. For evaluation of human exposure to such compounds, biological monitoring is an essential process, occupational and non-occupational exposure to PAHs can be monitored by measuring urinary PAH metabolits. In order to determine the method applicability, it was necessary to be validated. In addition, results of the analysis can be used as evidence in court. For this reason, method validation is very important.

In this study; as a marker urinary PAH metabolites exposure level, 1-hydroxypyrene (1-OHP), 3-hydroxybenzo[a]pyrene (3-OHBAP), and 9 – hydroxyphenantrene (9-OHPHE) levels were determined in urine. Assay method was performed by HPLC-FLD. For 1-OHP, 9-OHPHE and 3-OHBAP LOD and LOQ values were determined as 0.0077; 0.0033; 0.0031 and 0.0255; 0.0109; 0.0103 ng / mL urine, respectively. To determine the precision and accuracy of the present system, known high and low concentrations of 1-OHP, 9-OHPHE and 3-OHBaP were added to urine samples of non-smokers. The inter-day precision (repeatability) was determined by six-fold analysis of the urine sample. The spiked sample was analyzed six-fold on different days to evaluate the between days precision (reproducibility). The inter-day R.S.D. ranged between 2.02% (1-OHP) and 8.16% (3-OHBAP) and the between days R.S.D. ranged between 2,48% (1-OHP) and 12,85% (3-OHBAP). Recovery experiments were performed by addition of the standards to a 10 mL urine sample before the enzymatic hydrolysis. The recovery was in the range of 81, 88–97,70%.

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P41. PBDES: THEY ARE TOXIC AND THEY'RE EVERYWHERE

Nesrin ĠÇLĠ1* 1Ministry of Customs and Trade, Ankara Laboratory Directorate, Kazan, Ankara, TÜRKĠYE

Polybrominated diphenyl ethers (PBDEs) have been used as flame retardants for many years in such products as plastics, textiles, polyurethane foam and electrical equipment. PBDEs are environmental concern because of their high lipophilicity, and high resistance to degradation processes. Therefore, they are expected to readily bioaccumulation. It can be transported by air and water; have been found in invertebrates, fish, birds, marine mammals and humans. PBDEs elicit toxicity in mammals by binding to the transport proteins for thyroid hormones and thus altering thyroid homeostasis. Some hydroxylated polybrominated diphenyl ethers (HOPBDEs) have been identified as potential transformation products of polybrominated diphenyl ethers (PBDEs) and have been detected in human bodies which showed a more potent receptor activity compared to those of the parent PBDEs. PBDEs can be transformed by thermal recycling prosess into highly toxic compounds such as polybrominated dibenzofurans and dioxins (PBDD/Fs).

The European Union decided to ban the use of two classes of flame retardants, in particular, polybrominated diphenyl ethers (PBDEs) and polybrominated biphenyls (PBBs) in electric and electronic devices. This ban was formalised in the RoHS Directive, and an upper limit of 1 g/kg for the sum of PBBs and PBDEs was set. In the EU also the contents of decabromodiphenyl ether (DecaBDE) might not exceed 0.1% in EEE as set by the RoHS directive. At an international level, in May 2009 the Parties of the Stockholm Convention for Persistent Organic Pollutants (POPs) took the decision to list commercial penta-BDE and octa-BDE as POP substances.

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P42. ASSOCIATION BETWEEN HEAVY METALS AND SOIL PROPERTIES

Selma ÖZTEKĠN1*, Esma SÖYLEMEZ1 1Middle Black Sea Passage Generation of Agricultural Research Station Director, Tokat, TÜRKĠYE *[email protected]

The fate of heavy metal pollutants determines with mineral deposits, volcanic activity, industrial and municipal wastes, motor vehicle exhausts, sewage waters, unconsciously application of fertilizers and pesticides, faulty irrigations in the ecosystem. The amount of heavy metals in the soil depends on uptaken amount of heavy metals by plant, leaching and sorption. Some plant species prevents accumulation high levels of heavy metals in nature. Plants are accumulated heavy metals via roots to leafs and thus they are reduced heavy metal pollution in the soil. This period in plant are intensively affected by soil properties such as pH, organic matter contents, clay, hydrous oxides, and free carbonates, cation exchange capacity. In general, soil pH has important effect in the solubility or retention of heavy metals in soils. Heavy metals are a greater retention at high soil pH in soils. Organic matter has an essential role in agricultural processes. It increases cation exchange capacity and enhances soil fertility. Heavy metals by the effect on the activities microorganisms are effective in biological and chemical mechanisms in the soil. Also, metals are strongly adsorbed on the clay fractions and by hydrous oxides of iron, aluminum, manganese in soils. In this study, there will be discussed association between biological and chemical properties of soil with toxic levels of heavy metals found in soil.

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P43. PROTEINS SECONDARY STRUCTURES CHANGES IN PLEURAL FLUIDS DUE TO ASBESTOS-INDUCED LUNG CANCER

Sherif ABBAS1, Parvez I. HARIS2, Mete SEVERCAN3, Salih EMRI4, Feride SEVERCAN1* 1Middle East Technical University, Department of Biological Sciences, 06800, Ankara, TÜRKĠYE 2School of Allied Health Sciences, De Montfort University, The Gateway, Leicester, UNITED KINGDOM 3Middle East Technical University, Department of Electric and Electronic Engineering, 06800, Ankara, TÜRKĠYE 4HacettepeUniversity, Department of Chest Diseases, 06100, Ankara, TÜRKĠYE

Exposure to asbestos is carcinogenic to humans. Occupational and/or environmental exposure to asbestos can lead to the development of Malignant Pleural Mesothelioma (MPM). The main symptom of MPM is the accumulation of pleural fluid around the lungs. However the accumulation of pleural fluid could be due to other kinds of diseases such as inflammation. In order to identify whether the pleural fluid is due to MPM or other benign diseases, the details of pleural fluid‘s proteins content and their secondary structure has been studied using Attenuated Total ReflectionFourier Transform Infrared (ATR-FTIR) spectroscopy. For the analysis of proteins secondary structure from FTIR spectra, the amide I region(1700-1600 cm-1) was used.Wavelet analysis has been used to extract the Amide I spectral features.The extracted features were used as inputs for a previously trained Artificial Neural Networks (ANN) using protein infrared spectrato estimate protein secondary structure. The results show an overall increase of the protein content on the pleural fluid accumulated due to MPM relative to other benign diseases.Furthermore, an increase of β-sheet structure in the MPM pleural fluidwas found. This result could be attributed to an increase in proteins with β-sheetstructure and/or conformational changes resulting in increase of β-sheet structure of MPM pleural fluid.This study showed thatATR-FTIR spectroscopy in combination with a suitablefeatures extraction and classification methods can be a novel and rapid diagnostic method to differentiation of MPM from other benign diseases.

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P44. CHRONIC RADIODERMATITIS BY THE OCCUPATIONAL RADIATION ACCIDENT

Eylem DOGDU ġAHIN 1, Aslı AYTEKIN 1, MeĢide GÜNDÜZÖZ 1, Engin TUTKUN 1, Ömer Hınç YILMAZ 1 1Ankara Occupational Disease Hospital Ankara, TÜRKĠYE

Radiodermatitis, also known as radiation dermatitis can be either acute or chronic. The skin at the beam entrance place receives maximal radiation.Radiation-induced injury occurs instantaneously and it manifests as erythema, hair loss, dry or moist desquamation, erosion or sometimes bullous reaction.

Ir192 (iridium) source was commonly used in gammagraphic camera for industrial purpose. Ir192 source gammagraphic cameras are commonly used to check the integrityof welds in oil and gas pipes. A 27 year old male was industrial radiographer for 3 years. He wasn‘t educated for protective measures for ionizing radiation and did not wear protective gloves, eye glasses or clothes. He experienced an accidental exposure to ionizing radiation by Ir192during taking radiograph of natural gas pipes. In acute stage, his left finger became erythematous with blistering reaction and he complied about severe pain, numbness with tingling sensation and edema of the finger. Left finger of him was exposed repeatedly to radiation and cutaneous findings with fibrotic sequel were developed. We described a case of occupational chronic radiodermatitis by Ir192 source.

Patients with radiodermatitis also must be checked for systemic radiation injury and systemic cancer. Iridium 192 as a part of an industrial gammagraphy device was the source of accidental exposure in our patient. Ionizing radiation using industries should be aware of risk of accidental exposures. The workers such as industrial radiographers should be informed before beginning the work for protective measures. The safety parameters for ionizing sources must be checked.

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P45. NUTRITIOUS OR TOXIC? THE HIDDEN THREAT IN FOODS: BISPHENOL A (BPA)

Serpil KIRMIZI Ankara University, Institute of Forensic Sciences, Cebeci, Ankara, TÜRKĠYE

Today, adverse effects of Bisphenol A (BPA) which is generally used as an additive in plastic materials such as plastic bottles, plastic food containers, baby bottles and also some metal containers like tinned foods and beverages, to human health are being specified by several health organizations. Mostly the contamination of BPA in the foods is results of the migration from BFA included containers to foods. The way of entry of BPA to our bodies is generally consuming these contamined foods.

In recent years, observing the female early-puberties and the significant raise in the number of cancer cases in worldwide; BPA, whom estrogenic effects have been proved and counted as an environmental endocrine corruptive and is used as an additive in a lot of food and beverage containers, has become a major subject of several health researches.

In this review, BPA‘s contamination ways to foods, metabolic activities and the possible toxicologic effects on human bodies of BPA will be argued with the help of literature.

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P46. DETERMINATION OF CYTOTOXIC EFFECTS OF FIVE PHENOLIC COMPOUNDS IN V79 CELL LINE

Merve BACANLI1*, A. Ahmet BAġARAN2 and NurĢen BAġARAN1 1Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, TÜRKĠYE 2Department of Pharmacognosy, Faculty of Pharmacy, Hacettepe University, Ankara, TÜRKĠYE

Plant derived phenolic compounds in human diets can be found in significant amounts in many fruits and vegetables. According to the data obtained from previous studies, it is known that vegetables and fruits rich in phenolic compouns and other plant derived (liketeaandvine) diet would be protective against cancer and various diseases. It is suggested that phenolic compounds in plants were the main protective compounds and due to their cytotoxic effects on cancer cells, phenolic compounds have been found to have protective effects against cancer. Galangin, limonene, naringin, puerarin and ursolic acid are commonly used plant phenolics because of their health preventing effects. The aim of this study was to evaluate the cytotoxic effects of five commonly using phenolic compounds (galangin, limonene, naringin, puerarin and ursolic acid) by neutral red uptake (NRU) assay in Chinese hamster fibroblast cell line (V79). It is found that all of the studied phenolicsdecreased the cell viability of V79 cells in a dose dependent manner. The IC50 values of galangin, limonene, naringin, puerarin and ursolic acid were found to be 104,36 µM, 10574 µM, 1976,4 µM, 51,71 µM and 92,94 µM, respectively.

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P47. EVALUATION OF THE OXIDATIVE STRESS IN SILICOSIS PATIENTS

Kübranur ÜNAL ˡ, Bağdagül ÇAKIRˡ, Ceylan DEMIR BAL2, Ömer Hınç YILMAZ2, Engin TUTKUN2, Fatma Meriç YILMAZ1,3 1Ankara Numune Education and Research Hospital Biochemistry Department, TÜRKĠYE 2Ankara Occupational Diseases Hospital, TÜRKĠYE 3Yıldırım Beyazıt University Medical Faculty Biochemistry Department, TÜRKĠYE

Silicosis is a lung disease caused by the inhalation of free crystalline silica resulting in progressive massive fibrosis. In this study, we aimed to investigate serum TAS (Total Antioxidant Status), TOS (Total Oxidant Status) and OSI (Oxidative Stress Index) parameters in the individuals working in ceramic factory and diagnosed as silicosis and discuss the possible effects of these parameters on the etiopathogenesis of the disease.

This study was performed on 33 male patients with silicosis (23-73 years) and 30 male healthy controls (18-69 years). Plasma TAS, TOS levels were measured and OSI was calculated by the TOS/TAS formula.

Serum TOS levels of the silicosis subjects were higher than those of the controls whereas serum TAS levels of silicosis subjects was lower than that of the controls. But the differences between the parameters were not statistically significant. The serum OSI levels were significantly higher (p<0.05) in the silicosis subjects compared with the control group.

The exact mechanism of the silica toxicity of is still unknown. Silica particles are potent inducers of cell proliferation, cell injury, inflammation and release of free radicals from alveolar macrophages. Free radical generation by silica occurs via an oxidative burst when free crystalline silica are phagocytized by alveolar macrophages or other cell types, including alveolar epithelial cells and fibroblasts. Our study showed elevated OSI in patients with silicosis. Increased oxidative stress is thought to be related with the oxidative burst caused by alveolar macrophage activation.

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P48. DEATH DUE TO SUICIDAL ATTEMPT DEPENDING ON TAKING DRUGS CONTAINING PSEUDOEPHEDRINE SULFATE: CASE REPORT

1* 2 2 2 Semih PETEKKAYA , Nusret AYAZ , Mustafa DOĞAN , Mucahit ORUÇ , Bedirhan 1 1 2 1 Sezer ÖNER , Cihan GÖKTÜRK , Ahmet ÇELEBI , Adalet Eda BUDAK , Asım Cahit 3 2 ĠPEKÇĠ Osman CELBIġ 1 Council of Forensic Mortuary Department, Malatya, TÜRKĠYE 2 Department of Forensic Medicine, InönüUniversity, Malatya, TÜRKĠYE 3 Council of Forensic Chemistry Department, Malatya, TÜRKĠYE

Upper respiratory tract infections are common in the community and pseudoephedrine preparations are widely used in the treatment as a decongestant drug. Pseudoephedrine has serious side effects on the central nervous system and cardiovascular system. Infant death cases have been reported depending on the overdose in literature. Pseudoephedrine toxicity has not been observed adult suicidal purpose in literature. We present a case of 18 years old woman who taked pseudoephedrinesulfate preparation for suicidal attempt. The pseudoephedrine preparations are easily accessible and used widely. Also taking over dose pseudo ephedrine preparation can cause death in adults.

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P49. LEAD: ITS EFFECT ON FETUS AND INFANTS

Deniz KOCA, Dilek KAYA-AKYÜZLÜ Ankara University, Institute of Forensic Sciences, Ankara, TÜRKĠYE

Lead, the 5th most abundant metal in the earth‘s crust, is a naturally occurring, ubiquitous atmospheric pollutant. Humans can be exposed to lead through food, contaminated air and dust, and it accumulates particularly in the bones with a half-life of around 30 years. Lead has adverse effects to mainly renal, hematopoietic and neurologic systems and the most susceptible populations to the adverse neurodevelopmental effects of lead are children, particularly infants in the neonatal period and fetus as neurodevelopment begins in this period and the blood-brain barrier is still immature. Moreover, exposure levels that do not harm the mother can be fetotoxic because of the differences between the many biochemical pathways of the adult and the fetus. Lower IQ, reduced frustration tolerance, attention deficit, hyperactivity and weak reaction control are possible neurodevelopmental consequences of lead exposure. Fetal exposure to lead begins at the 21st week of pregnancy and continues throughout the life. This may lead to chronic diseases either immediately or later in life. Thus, pregnancy and the first 2 years of life are exceptionally important intervals with respect to adequate maternal and child nutrition. Although the placenta, an interface between the developing fetus and the mother, has mechanisms that restrict the entry of toxicants, it cannot protect the fetus from exposure to lead from mother‘s blood. Lead exposure during pregnancy has been shown to increase the risk for abortions, premature births and prenatal deaths. Developmental delay has also been found in infants with evidence of high lead levels in maternal and fetal blood.

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P50. TOXICOLOGY, PHARMACOLOGY, DETECTION AND LEGAL STATUS OF SYNTHETIC CANNABINOIDS

Sezen YILMAZ, Merve DEMIRBUGEN, Can Ozgur YALCIN Ankara University, Faculty of Pharmacy, Department of Pharmaceutical Toxicology, TÜRKĠYE

Synthetic cannabinoids (SCs) which are derivates of delta-9-tetrahydrocannabinol (THC) have been problematic over the years and marketed as all naturel herbal blends and commonly abused by smoking like marijuana. They also known by the name of ―Spice‖, ―K2‖or ―Bonzai‖ which is sought by users for its THC like psychoactive effects and minimal legal regulations, perceived safety profile and lack of detection on routine urine screen tests.

The toxic effects of the SCson central nervous system (such as agitation, confusion, anxiety, hallucination, paranoia, tremor, seizures and vomiting) and cardiovascular system (rapid heart rate, high blood pressure, myocardialischemia, heartattack, tachycardia) are the most common reasons for emergency medica ltreatment, which in some cases can be severe and even life- threatening. The purpose of this review is to understand the pharmacokinetic, pharmacodynamic effects, detection, monitoring and legal status of SCs.

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P51. THE EFFECTS OF CHEMICAL RISKS INTEXTILE INDUSTRY ON WORKERS’ HEALTH

Filiz AYDIN*, Filiz DEREKAYA Faculty of Engineering, Department of Chemical Engineering, Gazi Univesity, Ankara, TÜRKĠYE *[email protected], [email protected]

In the textile industry, the part that has the most of the chemical risks is the colouring operations. Generally, chemicals are being used in operations which are called finishing pretreathment (cleaning, eaching, whitening etc.) dyeing, printing and finishing parts in addition to removals of stains and drying of the products. During the process, chemicals such as halogenated hydrocarbons, olefins, acids may occur. Use of in powder form and inhalation by the workers is very dangerous. Serious problems can occur in cases of contact with skin and eyes that the solvents, acid, bas and salts used in the textile industry. The most of surfactants such as antifoaming agents, washing agents, wetting agents use in textile finishing are found in a form of mixture and they are harmful to health when they are used without proper knowdge about them. Improving knowledge about chemicals that have been harming workers‘ health and their effects, will increase the level of precautions during the usage and occupational safety, and will have positive reflections on environment. The purpose of this study to draw attention to the textile chemicals used during manufacturing process to the effects on worker health and to raise level of perception in their use. In this study a comprehensive literature search was conducted, as a result the health effects of chemicals used in the textile industry and measures to be taken against them were given.

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P52. A CASE OF SUDDEN DEATH DUE TO LIGHTER REFILLGAS INHALATION

Semih PETEKKAYA1*, Nusret AYAZ2, Mustafa DOĞAN2, Mucahit ORUÇ2, Bedirhan Sezer ÖNER1, Cihan GÖKTÜRK1, Ahmet ÇELEBi2, Adalet Eda BUDAK1, Özcan SOYLU3 Osman CELBIġ2 1Council of Forensic Mortuary Department, Malatya, TÜRKĠYE 2Department of Forensic Medicine, Inönü University, Malatya, TÜRKĠYE 3Council of Forensic Chemistry Department, Malatya, TÜRKĠYE

Butane is found in lighters refill, which is a colourless and flammable gas with a gasoline-like or natural gas odour. The using of easily accessible lighter gas butane is increasing among children and adolescants cause of its euphoric effects. Among adolescents inhalants are the most commonly used drug, except for alcohol and tobacco. In literature after butane inhalation it has been reported cases of central nervous system, respiratory and cardiovascular system affected. We present a case of sudden death due to seventeenyears old male inhalated butane containing lighter refill gas to get her with two friends, and findings of autopsy, toxicology and histopathology investigations.

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P53. A REVIEW OF EFFECTS OF MORPHINE ON DEVELOPMENT OF DIPTERAL LARVAE IN MORPHINE RELATED DEATHS

H. Nihal AÇIKGÖZ1, UlaĢ SAĞDUYU2 1Ankara University, Forensic Sciences Institute, Forensic Biology Department, Ankara, TÜRKĠYE 2Ankara University, Forensic Sciences Institute, Physical Examinations and Criminalistic Department, Ankara, TÜRKĠYE

Forensic entomotoxicological methods are used in practice to detect and to identify narcotics including morphine, heroin and cocaine in deaths from these substances and drugs in deaths from deliberate and accidental intake of drugs and to determine the time of death. Necrophage insects are reliable material in toxicological analyses in cases in which conventional specimens including blood, urine and internal organs cannot be used as a result of putrefaction occurring after death. The aim of this review is to emphasize the importance of effects of morphine on development of blowfly larvae and on determination of post-mortem intervalin forensic cases. The key words ―morphine and blowfly‖ were used and all articles including these keywords, written in English, published between 2000 and 2014 and found in National Library of Medicine‘s PubMed Medline database were obtained. Effects of morphine on the development of blowfly larvae were examined based on results of the studies reported in the obtained articles. The results of the studies showed that morphine slowed down the life cycle of Lucilia sericata, but accelerated that ofChrysomyia megacephala. Differences in effects of morphine on life cycles of different species must be evaluated carefully. Since tissue specimens appropriate for toxicological analyses cannot be found on corpses in deaths suspected of being caused by drugs, larvae on these corpses should not be disregarded. They should be collected and exposed to toxicological analyses. It should be kept in mind that different Dipteran species can react to the same drug differently, which can be a very important criterion in an accurate determination of post mortem interval.

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P54. PHTHALATE TOXICITY AND EXPOSURE PATHWAYS

Emrah DURAL*, Zeliha KAYAALTI, Ferda Ceren ġAHIN Institute of Forensic Sciences, Ankara University, TÜRKĠYE

Phthalates, or the phthalate esters, are a group of industrial chemicals largely used in general consumer products including plasticizers, additives and solvents; in applications that include building materials, clothing, , perfumes, lubricating oils, solvent, detergents, food packing, toys, vinyl products; in medical applications that include blood transfusion bags and tubing, intravenous fluid bags and tubing, and other medical devices. Some phthalates are reported as carcinogenic, reproductive, and developmental stimulator in animal experiments. Diethyl phthalate (DEP) induce toxicity in the liver and kidney, also related maternal exposures. In addition, DEP exposure may also alter reproductive parameters. Dimethyl phthalate (DMP) induce decrements in body weight gain, changes in hemoglobin, and increases in absolute and relative liver weight. Benzyl butyl phthalate (BBP) have a weak estrogen activity at high exposure concentration. Bis(2-ethylhexyl) phthalate (DEHP) produce a wide range of adverse effects in experimental animals, notably liver toxicity and testicular atrophy. The toxic and carcinogenic effects of DEHP have been well established in experimental animals. Humans can be exposed to phthalates via ingestion, inhalation, dermal routes, as well as intravenous and parenteral absorptions. Phthalates are rapidly metabolized to their respective monoesters, after exposures. These monoesters may be further metabolized by oxidation and/or glucuronidation and excreted in urine and feces. The measurement of monoester phthalates metabolites in urine and serum used as biomarkers of exposure to phthalates.

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P55. THE POTENTIAL ROLE OF CYP2D6 PHARMACOGENETICS IN FORENSIC TOXICOLOGY

Zuhal UÇKUN1*, Sinan SÜZEN2 1Department of Toxicology, Faculty of Pharmacy, University of Mersin, Mersin, TÜRKĠYE 2Department of Toxicology, Faculty of Pharmacy, University of Ankara, Ankara, TÜRKĠYE

Pharmaceutical drugs have been commonly implicated in drug-related deaths. Polymorphism in the genes encoding drug-metabolizing enzymes could lead to therapeutic failure or severe toxicity, even to death by altering the relationship between dose and plasma drug concentration. The cytochrome P450 (CYP) enzymes are responsible for the metabolism of a large number of drugs. Approximately 25% of all drugs in human liver are metabolized by CYP2D6. CYP2D6 is the most polymorphic CYP enzyme. CYP2D6 gene consists 9 exons encoding a polypeptide of 497 amino acids, and to date, at least 104 allelic variants (*1B through *105) of the CYP2D6 gene have been described and almost 20 of them significantly affect the metabolism of drugs that are substrates for this enzyme. Phenotyping for CYP2D6 have four types of metabolizers – Ultra Rapid Metabolizers (UMs; CYP2D6XN), Extensive Metabolizers (EMs; CYP2D6 *2, *33, *35); Intermediate Metabolizers (IMs: CYP2D6*9, *10, *17, *36 and *41); Poor Metabolizers (PMs: CYP2D6 *3, *4, *5 and *6). PMs have at increased risk of suffering from adverse side effects due to drug overdose or of experiencing therapeutic failure due to poor metabolism of a prodrug to the active metabolite. Conversely, UMs have significantly increased enzyme activity. So that, they may experience either subtherapeutic blood levels of the enzyme substrate or adverse side effects because of ultra- rapid metabolism of a prodrug to the active metabolite. As a result, pharmacogenetic analysis may reveal new insight to the interpretation of forensic toxicological results.

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P56. INVESTIGATION OF GENOTOXIC ACTIVITIES OF PARABEN IN HUMAN LYMPHOCYTES

Devrim GÜZEL*, Gülsüm Handan SINAN AYDIN, Berrin AYAZ TÜYLÜ 1Department of Biology, Faculty of Sciences, Anadolu University, Eskisehir, TÜRKĠYE

Paraben is a monohydroxybenzoicacid, a phenolic derivative of benzoicacid. That is extensively used as preservatives in the food, pharmaceutical and cosmetic industries due to its antimicrobial characteristics. Paraben‘s toxic and genotoxic effects are very important for human health because of these compounds is used so much in daily life. The aim of this study to investigate the in vitrogenotoxic effects of paraben in healthy human lymphocyte cultures. So that the genotoxic effects of parabenwere investigated after 24 and 48 hours treatment with cultured human lymphocytes with Cytokinesis Blocked Micronucleus (CBMN) assay and Chromosome Aberration (CA) methods in vitro. Also DNA damage was measured using the Comet Assay in isolated human lymphocytes exposed to different concentrations and 1 hour treatment of paraben. According to the values, paraben caused dose and time dependent increase in MN frequency and dose and time dependent decrease in cell proliferationindex (CBPI) in CBMN assay. Also in chromosome aberration assay, paraben induced hromosome breaks and decreased mitotic index all concentrations and all treatment times when compared with control. In the comet assay, significant DNA fragment migration was observed especially in paraben‘s high doses.

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P57. OXIDATIVE STRESS STATUS IN LEAD EXPOSED WORKERS

Esra FIRAT OĞUZ1, Esin ÇALCI1, Ceylan DEMIR BAL2, Ömer Hınç YILMAZ2, Engin TUTKUN2, Fatma MERIÇ YILMAZ1,3 1Ankara Numune Education and Research Hospital Biochemistry Department, TÜRKĠYE 2Ankara Occupational Diseases Hospital, TÜRKĠYE 3Yıldırım Beyazıt University, Medical Faculty Biochemistry Department, TÜRKĠYE

Lead is a widespread heavy metal that can persist in water, plants and soil in environment naturally. When it is used in some industries, it turns to destructive and toxic form. Human exposure can be associated with the use of lead containing ceramic dishware, food cans and paints besides the exposure in the workplace. One of the most possible mechanisms that cause Pb-induced toxicity is oxidative stress. We aimed to evaluate TAS (total antioxidant status), TOS (total oxidant status) and OSI (oxidative stres index) levels in patients with lead exposure.

30 workers with chronic lead exposure who admitted to Ankara Occupational Diseases Hospital and 35 healthy controls were included in the study. The workers were from 50% battery (n=15), 30% welding (n=9) and 20% recycling (6) factories. TAS, TOS levels were measured in blood samples and OSI was calculated according to formula (TOS/TAS).

TOS levels were significantly higher in patient group (p=0.001). There was no significant difference in terms of TAS levels. Calculated OSI levels were significantly higher in patient group (p<0.001).

Our data confirms that lead exposure is associated with incerased oxidative stress. TAS, TOS and OSI levels can be used to evaluate antioxidant-oxidant balance in lead exposure.

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P58. ASSESSMENT OF CA125 AND CA19-9 IN SILICOSIS

Bağdagül ÇAKIR1, Kübranur ÜNAL1, Ceylan DEMIR BAL2, Ömer Hınç YILMAZ2, Engin TUTKUN2, Fatma MERIÇ YILMAZ1,3 1Ankara Numune Education and Research Hospital Biochemistry Department, TÜRKĠYE 2Ankara Occupational Diseases Hospital, TÜRKĠYE 3Yıldırım Beyazıt University Medical Faculty Biochemistry Department, TÜRKĠYE

Silicosis characterized by the development of pulmonary fibrosis with progressive impairment of pulmonary function is caused by the inhalation of silica particles. The serum tumor markers, because of several immunological and inflammatory functions have been shown to be increased in non-malignant lung diseases.This study was designed to investigate the clinical significance of tumor markers in patients with silicosis.

29 male patients aged between 23-73 diagnosed with occupational disease related to silica intoxication in Ankara Occupational Diseases Hospital and age/sex-matched control group consisted of 30 healthy volunteers were recruited. Silicosis patients were diagnosed depending on their chest radiograms in accordance with the ILO2000 guidelines. CA19-9 and CA125 concentrations were detected in fasting sera using chemiluminescence enzyme immunoassay.

The serum tumor marker concentrations of patients with silicosis were compared with healthy controls. Patients with silicosis had significantly higher (p<0,05) levels of CA125 (10,95 U/mL (0,8-76,80) than controls (8,65 U/mL (3,50-20,30)). However, there were no significant differences in CA19-9 between the groups (p >0.05)

CA125 is expressed by tissues including the mesothelial lining cells of peritoneum, pleura, and pericardium. Any physiologic or pathologic reactions of these cells cause an increase of serum CA125 level. Chronic inflammation of mesothelial cells of pleura may also cause a similar response. Inflammation also plays an important role in the development of silicosis. Increased CA125 concentrations in silicosis are possibly associated with inflammation and seem to be a possible biomarker to be used in silicosis patients.

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P59. DICLE UNIVERSITY MEDICAL SCHOOL HOSPITAL EVALUATION OF NARCOTIC SCREENING

Sefa ÇIFTCI¹*, Seyyit KUġ², Hatice YÜKSEL², Hüseyin Tuğrul ÇELIK¹, Mehmet NAMUSLU¹, Fatmanur HACIEVLIYAGIL KAZANCI¹, Yunus Emre BILGEN¹, Selahattin ARTUdz 1Department of Medical Biochemistry, Turgut Ozal University School of Medicine, TÜRKĠYE 2Department of Medical Biochemistry, Dicle University Faculty of Medicine, TÜRKĠYE 3Department of Forensic Medicine, Selcuk University Faculty of Medicine, TÜRKĠYE

Since the beginning of human history, narcotics are used as painkiller, pleasant and healing diseases. In consumption due to the pleasing feature has been a significant increase in the historical process. This narcotic is being added to new every day, made it mandatory screening tests. In this study we investigated narcotic scan results.

Narcotics scan results were analyzed retrospectively at the Department of Biochemistry in Dicle University Medical Faculty between April 2014 and October 2014. In our study, we evaluated 11 narcotics (Barbiturate, Benzodiazepine, Morphine/Opitates, Marijuana, Mdma/xtc, Cocaine, Tricyclic, Amphetamine, Methadone, Methamphatemine, Phencyclidne).

625 patients narcotic scans were performed between 1 April 2014- 1 October 2014. Screening results of 365 (58.4%) negative, 260 (41.6%) were positive. In the positive; the number of male patients 229 (88%), the number of female patients 31 (12%) and mean age of 26 (range 14-64 years) were found. According to the scanning results the most frequently substance marijuana (44.3%), 2nd often benzodiazepine (11.4%) and 3rd often tricyclic agents (9%) were found. Other substances were detected lesser amounts.

As in all the world, drug addiction is increasing rapidly day by day in Turkey. According to the latest reports, in our country has been reported that marijuana is the most commonly used narcotic. This study has shown that marijuana is the most commonly used drugs.

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P60. SERUM S100B, NEURON SPESIFIC ENOLASE (NSE) and GLUTAMATE RECEPTOR 1(GRIA) LEVELS AS NEUROLOGICAL MARKERS in LEAD EXPOSURE

Esra FIRAT OĞUZ1, Fatma Meriç YILMAZ1,2, Engin TUTKUN3, Hınç YILMAZ3, Sevilay SEZER1 1Clinical Biochemistry, Ankara Numune Education and Research Hospital, TÜRKĠYE 2Yıldırım Beyazıt University Medical Faculty Biochemistry Department, TÜRKĠYE 3Ankara Occupational Diseases Hospital, TÜRKĠYE

Central nervous system is a major target in lead exposure. Markers for the diagnosis and follow up of lead exposure have not been identified. In this study, serum S100 B, neuron specific enolase (NSE) and Glutamate Receptor 1 (GRIA) levels were determined as possible markers for lead neurotoxicity

25 patients with chronic lead exposure and 25 controls were included in the study. NSE and S100B were measured by elechtrochemiluminescence immunoassay in Cobas E601 analyzer. GRIA levels were measured by Cusabio brand ELISA kit using quantitive sandwich enzyme immunoassay technique.

GRIA levels were significantly higher in patient group than in control group (p=0,011). No significant difference was determined between the patient and the control group in the name of NSE, S100B, ALT, AST and creatinine levels (p>0.05). There was not a significant difference between neurological sign positive and negative groups in any of the studied parameters.

Patients with chronic lead exposure are found to have increased glutamate receptor levels and do not seem to have glial and neuronal damage which can be demonstrated with the elevation of NSE and S100 B levels. Glutamate signaling pathways might be the major affected side in chronic lead exposure and can be used as a marker for the neurotoxicity of lead.

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P61. DNA METHYLATION STATUS IN EXPOSURE TO INDUSTRIAL SOLVENTS AND METALS

AyĢegül YÜKSELTÜRK1, Asuman ÖZGÖZ2, Engin TUTKUN3 1Kastamonu University, Fazıl Boyner School of Health, Kastamonu, Department of Nutrition and Dietetics, Kastamonu, TÜRKĠYE 2Kastamonu University, Fazıl Boyner School of Health, Kastamonu, Department of Nutrition and Dietetics, Kastamonu, TÜRKĠYE 3Department of Occupational Toxicology, Ankara Occupational Diseases Hospital, Ankara, TÜRKĠYE

In working places there are acute and chronic effects due to occupational exposures and solvent or metal toxicology concerns safety of working place besides public health. These exposed molecules cause pathologic effects in cell cycle and gene expression by increasing inflammational response, inhibiting antioxidant mechanisms of cells, causing lipid peroxidation and inhibiting DNA repair. Recent studies focused on various solvent and metal exposures and alterations in DNA methylation status.

DNA methylation plays a regulator role in general and regional stage. Especially CpG dinucleotides in highly repetitive DNA sequences such as satellite DNA play an important role in genomic stability. Alterations in DNA methylation as regional hypermethylation or hypomethylation are reported to be related to many diseases. In many studies about the role of epigenetics in human diseases focused on the relation between alterations in DNA methylation and diseases and environmental effects on DNA methylation variations.

It is reported that there is a relation between many environmental agents such as toxins, stress, heavy metals and epigenetic alterations. Until today in some of the studies, DNA methylation stages were determined in people exposed to many occupational chemicals. However there are not many studies investigating DNA repair gene methylations in occupationally exposed groups. Usage of DNA methylation as a biomarker for people with environmental or occupational exposure may be important for determining workers under risk and taking precautions.

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P62. ROLE OF THE KAEMPHEROL ON THE ANTI TUMORAL EFFECTS OF DOXORUBICIN IN HEPATOCELLULAR CARCINOMA (HCC)

E. ERDAĞ1*, E. ERGENE1 1University of Anadolu, Faculty of the Sciences, Department of Biology, EskiĢehir, TÜRKĠYE

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. This cancer heads the list of cancer-releated deaths in the world. Doxorubicin (Dox) is anti- tumor drug frequently useds in the treatment of various cancers, especially liver cancer. However, Dox have organo toxic effects and is also resistant to many cancer cells including HCC. Therefore; Dox‘s clinical applications are limited. Kaempferol (Kæmp) as a natural polyphenol component has broad pharmacological activity. Consumption of food with Kæmpe reduces the risk of many diseases such as cancer and leads to apoptosis in various cancer cells.

In this study; independent and combined effects of the Kaemp were investigated on the Dox‘s anti-cancer (cytotoxicandapoptoticect.) effects in hepatocellular carcinoma cells (Hep-G2). Cytotoxic effects of the Dox, Kaemp and combination were determined by MTT assay. Apoptotic effects were determined by a morphological assay as Acridin Orange/Ethidiım Bromide (AO/EB) double staining. As apoptosis markers, changes in enzyme activitiesof Caspase 3 and Caspase 9 were analysed.

The viability of the Dox-treated Hep-G2 cells were decreased, in a dose-and time- dependent,at 48 hours and the IC50 value was determined to be 0,5 µM. Kæmp‘s IC50 value found to be approximately 100 µM at 48 and 72 hours. As compared with Dox, the cytotoxic effect of the Kæmp was observed at approximately 100-fold weaker in Hep-G2 cell lines. As a result of the AO/EB double staining; 100 and 150 μM Kæmand 0.5 μm Dox caused apoptosis. In combination treated cells early apoptotic cells was observed and when applied Kζmp 150 μM, a significant increase was observed in the number of necrotic cells. In addition, changes in enzyme activation of Caspase 3 and 9 were determined in Hep-G2 cells.

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P63. THE IMPACT OF NOISE POLLUTION ON HUMAN HEALTH

Sakine UGURLU KARAAĞAÇ* Karabük University, Engineering Faculty, Environmental Engineering Department, Karabük, TÜRKĠYE *[email protected]

Noise is define as any undesirable human or machine created noise which disturbs the activity or balance of human or animal life. In simple terms, noise is unwanted sound. Sounds produced by all vibrating bodies are not audible. The Intensity of Sound is measured in terms of sound pressure level and common unit is decibel. Thus dB measures how much intense is the sound as compared to reference intensity.

A noise problem generally consists of three inter-related elements: a) the source, b) the receiver, c) the transmission path. Major sources of noise: Traffic noise,air crafts creates serious problems in big cities. Heavy truck, buses, trains, motorcycles, jeeps, other vehicles are responsible for traffic noise. Industrial and construction machinery noise: Factory equipment, generators, drills, road rollers, and similar machinery also make lot of noise Noise health effects are the health consequences of elevated sound levels. Elevated workplace or other noise can causehearing impairment, hypertension, ischemic heartdisease, annoyance, and sleep disturbance. Changes in the immune system and birth defects have been attributed to noise exposure. Noise exposure also has been known to induce tinnitus, vasoconstriction, and other cardiovascular adverse effects.Excessive noise seriously harms human health and interferes with people‘s daily activities at school, at work, at home and during leisure time. It can disturb sleep, causes cardiovascular and psychophysiological effect, reduce performance and provoke annoyance responses and changes in social behavior

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P64. OXIDATIVE STRESS STATUS IN WORKERS WITH TOLUENE EXPOSURE

Nihal BOĞDAYCIOĞLU1, Alper KÜTÜKÇÜ1, Ceylan DEMIR BAL2, Ömer Hınç YILMAZ2, Engin TUTKUN2, Fatma MERIÇ YILMAZ1,3 1Ankara Numune Education and Research Hospital Biochemistry Department, TÜRKĠYE 2Ankara Occupational Diseases Hospital, TÜRKĠYE 3Yıldırım Beyazıt University Medical Faculty Biochemistry Department, TÜRKĠYE

Polycyclic aromatic hydrocarbons (PAHs) are well-known group of chemical carcinogens and can cause environmental pollution. Toluene is a polycyclic aromatic hydrocarbon which is found in plastics, paints and solvents like benzene. In this study, we evaluated the association between toluene exposure and TAS (Total Antioxidant Status), TOS (Total Oxidant Status), OSI (Oxidative Stress Index) measurements in workers with toluene exposure. The workers with toluene exposure were admitted to Ankara Occupational Diseases Hospital from 46.6 % painting (n=14), 33,3 % automotive and repair (n=10) and 20% furnishing (n=6) sectors. Oxidative stress status was evaluated using TAS, TOS, OSI markers in 30 toluene exposed workers and 30 control subjects. OSI was calculated by the TOS/TAS*100 formula.

TOS levels and OSI value in toluene exposed group were significantly higher (p=0.017, p=0.013; respectively) and TAS levels were significantly lower (p=0.040) than the control subjects.

Our study showed that toluene exposure cause increased oxidative stress. Taking measures to reduce exposure to toluene may reduce incidence and severity of oxidative stress based diseases like cancer, inflamatuar disease, infection and aging.

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P65. SUCCESSFUL TREATMENT OF A BELLADONNA POISONING WITH PHYSOSTIGMINE

Semih DEĞERLĠ, Gökhan YILDIZ, Eyup HORASANLI Keçiören Training and Research Hospital, Anesthesiology and Reanimation Clinic, TÜRKĠYE

Belladonna is a poisonous plant. Because plant leave sand fruits highly contain atropine alkaloids such as scopolamine and hyoscyamine. These alkaloids, competitively inhibits muscarinic receptors in the central nervous system. Also post ganglionic muscarinic receptors are affected. Blocking of these receptors leads to clinical manifestations that may lead convulsions and coma. Sometimes it can also manifestit self with psychosis and hallucinations. In this case, we present a patient who admitted to the emergency room with hallucinations after eating plenty of belladonna berries. A 23-year-old male patient was admitted to emergency department with complaints of hallucinations and deterioration in the general condition. Glasgow coma scale (GCS) was 13. Arterial blood pressure, heart rate, respiratory rate, temperature were 150/75 mm Hg, 101 / min, 17 / min. and 37 C respectively. He did not have any additional disease. But approximately 8 hours ago she had eaten black fruits during the picnic. Later it was noticed that the fruits were belladonna. The patient was in an anticholinergic toxic condition. Patient's stomach was aspirated with a nasogastrictube after irrigation with isotonic saline. Then activated charcoal 1 mg / kg was administered. Physostigmine 1 mg was administered with recommendation of the National Poison Control Center in ICU. After a total 4 mg physostigmine consciousness was recovered and hallucinations were resolved completely. One day later the patient was transferred to the ward without any problem. Medical history of the patients with anticholinergic symptoms should be taken very cautiously. Inparticular, the comatose or confused patients should be quickly followed under intensive care conditions. Also physostigmine should be immediately administered after gastric lavage as an early treatment. As in our patient, we believe that early application of physostigmine and gastric lavage are life savers.

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P66. DUAL PURPOSE REAGENTS FOR DIAGNOSIS OF AMINO ACID DISORDERS

Serkan GÜRBÜZ, Melek EROL* Chemistry Institute, TUBITAK Marmara Research Center, Gebze, Kocaeli, TÜRKĠYE *[email protected]

We report on the selectivity of several amino acid sensitive molecules towards different amino acids, especially the ones present in latent fingermarks. Florescence and color formation of six different amino acid reactive reagents (genipin, ninhydrin, lawsone, 5- hydroxy-1,4-naphthoquinone (juglone), 2-methoxy-1,4-naphthoquinone and 1,2- naphthoquinone-4-sulfonate) when reacted with L-alanine, L-glycine, L-cysteine, L-histidine, L-serine and L-aspartic acid on filter paper as a function of amino acid concentration, temperature and reaction time were studied. Fluorescence spectra were collected at excitation wavelengths of 505-590 nm.

Orange or purple color formation was observed for all samples when the active reagent treated amino acid spots (10 mM) heated at 150 °C for 1 hour. While intense color and florescence was observed with all dual purpose reagents towards L-histidine, juglone formed a non-fluorescent blue color with L-cysteine under these conditions. Increasing the heating time usually increased the color contrast, but it decreased the fluorescence of the spots.

The fluorescent character was decreased in the following order: genipin > juglone > 2- methoxy-1,4-naphthoquinone > lawsone > 1,2-naphthoquinone-4-sulfonate > ninhydrin when the amino acid spots were heated at 150 °C for 1 hour after treatment with 1 mM active reagents. Fluorescence of real fingerprints developed on paper surfaces using different active reagents was also compared.

Results reported here would play an important role in the detection and diagnosis of amino acid disorders such as phenylketonuria in the presence of abnormal amount of specific amino acids in the fingerprint secretions, blood or other body fluids.

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P67. CYTOTOXICITY OF CADMIUM CHLORIDE IN VERO CELLS AND PROTECTIVE EFFECTS OF GLUTATHIONE, N-ACETYLCYSTEINE AND CATALASE

Duygu PASLI, Aylin GÜRBAY* Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Ankara, TÜRKĠYE

Cadmium is an environmental pollutant with well-known nephrotoxic effects. The present study was designed to evaluate the possible time- and dose-dependent cytotoxic effects of

cadmium chloride (CdCl2) to African green monkey kidney normal cell line (Vero cells). The cultured cells were exposed to 11 different concentrations of cadmium chloride ranging from 0.05 to 300 µM for 24, 48 and 72 h and cytotoxicity was determined by MTT assay. Possible protective effects of glutathione (GSH), N-acetylcysteine (NAC), and catalase against cytotoxic effect of CdCl2 were also tested. Our results revealed that the effect of CdCl2 on viability of Vero cells was concentration- and time-dependent. Exposure of cells to ≥40 µM CdCl2 for all incubation periods caused significant decrease in cell survival. Pretreatment of cells with GSH, NAC or catalase for 4 h provided protection against CdCl2-induced cytotoxicity following 48 h. Spectrofluorometric assessment of the level of reactive oxygen species (ROS) using a fluorescent probe 2′,7′-dichlorofluorescein-diacetate (DCFH-DA) indicated production of ROS in this system. The data obtained in this study suggest that, in accordance with literature, CdCl2-induced cytotoxicity is related to oxidative stress.

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P68. FGFR1 SER777 MUTATION AND BLADDER CANCER

Asuman ÖZGÖZ*1, Hale ġAMLI2, Murat ġAMLI3, Deniz DINÇEL2, Ümit ĠNCE4, Ahmet ġAHIN3 1Kastamonu University, Fazıl Boyner School of Health, Kastamonu, Department of Nutrition and Dietetics, Kastamonu, TÜRKĠYE 2Uludag University, School of Veterinary Medicine, Department of Genetics, Bursa, TÜRKĠYE 3Acıbadem University, School of Medicine, Department of Urology, Istanbul, TÜRKĠYE 4Acıbadem University, School of Medicine, Department of Pathology, Istanbul, TÜRKĠYE

Bladder cancer is the fourth most frequent cancer type among men and eighth most frequent among women in western countries. As fibroblast growth factor receptors (FGFRs), receptor tyrosine kinases are related to many cancers and different pathological situations. Therefore FGFRs‘ regulatory mechanisms are needed to be understood and are in current interest. The four closely related FGFR receptors (FGFR1 to FGFR4) have important duties in proliferation, differentiation, migration, and survival of cells.

Because FGFR1 C-terminal including amino acids 755 to 822 has many serines; it is suggested that FGFR signaling might be regulated via specific serine phosphorylation and wild-type FGFR1 was detected to be phosphorylated by active ERK1 and ERK2 forms but FGFR1 critical serine mutated proteins at the S777A and S777D, were not. FGFR1 ser 777 was shown to be mutated in a few number of research that has been carried out in the area of cancer . But these mutations was shown only in cell lines and and not by directly sequencing or controlling of the mutation as nucleotide change. In our study, FGFR1 ser 777 mutation was studied by sequence analysis method in 62 cases with bladder cancer and in 30 healthy controls.

In the study we performed, there was any FGFR1 ser 777 mutation neither in case nor in the bladder cancer group. It may be concluded that ser 777 is not mutated in bladder cancer.

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P69. ASSESMENT OF IN VITRO GENOTOXIC ACTIVITIES OF SOME TRIMETHOPRIM SALTS

Devrim GÜZEL1*, Berrin AYAZ TÜYLÜ1 1 Anadolu University, Faculty of Science, Dept. of Biology, Eskisehir, TÜRKĠYE

Trimethoprim is a commonly used antibacterial substance which is used extensively in the treatment of various infections in humans. The purpose of this study is to determine the genotoxic activities of trimethoprim, trimethoprim+maleic acid, trimethoprim+oxalic acid dihydtrate. Cytogenetic alterations in cultured peripheral blood lymphocytes such as micronuclei (MN) which originate from chromosomal fragments or chromosomes are biomarkers of genotoxic exposure and early effects of genotoxic carcinogens .So that reason, the genotoxic effects of these compoundswere investigated after 24 and 48 hours treatment with cultured human lymphocytes with Cytokinesis Blocked Micronucleus (CBMN) assay. According to our results, trimethoprim and its salts have statistically increased micronucleus frequency dose and time dependent in human peripheral lymphocytes. From the results obtained, it appears that these drugs are able to induce genotoxic damage on human peripheral lymphocytes.

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P70. THE CYTOTOXIC EFFECTS of DURSBAN 4 INSECTICIDE on ALLIUM CEPA MERISTEM CELLS

Serap TOPCU 1, Sema (TAN) CETĠN2, Aysun ERGENE2 1Ankara University, The Institute of Forensic Sciences, Dikimevi, Ankara, TÜRKĠYE 2Kirikkale University, Department of Biology, Yahsihan, Kirikkale, TÜRKĠYE

Pesticides are chemical substances, that remove and destroy microorganisms, insects, weeds, fungi cause a loss of product during production, consumption and storage of agricultural products, regulate plant growth by improving quality and productivity. Commonly used pesticides lead a negative impact on health, environment, and economy of a country. It has been identified that pesticides have effects stoper the development, disease-causing, genotoxic, mutagenic, carcinogenic and even lethal effects on especially creatures are not target with in vivo and in vitro studies. In TÜRKĠYE, the most commonly used type of pesticides ise insecticide and it creates the dangerous toxic impact on plants. Therefore, pesticides play an important role in toxicology.

In this study, the cytotoxic effects of ―Dursban 4‖ insecticides on Allium cepa (onion) root cells were investigated. It is investigated that mitosis and chromosome damage and micronucleus formation on onion root cells growed in a concentration of insecticide 600, 1200, 1800 ppm solution. Germinating onion root cells at the specified concentrations have been fixed, dyed and examined under light microscopy. As parallel with the increase in concentration of Dursban 4, the chromosome breakage, chromosome stickiness, track formation, chromosome loop, delayed and irregular chromosome distributions were determined in the root tip meristem cells.

As a result, it is determined that attempted concentrations of ―Dursban 4‖ insecticide adversely affected Allium cepa chromosome and stimulated the formation of micronucleous.

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P71. DETERMINATION OF PETHIDINE IN URINE AND ITS RECOVERY EFFICIENCY

Zeynep TÜRKMEN1*, Selda MERCAN1, Murat YAYLA1, IĢıl BAVUNOĞLU2, Münevver AÇIKKOL1 1Istanbul University, Institute of Forensic Sciences, 34303, Cerrahpasa, Istanbul, TÜRKĠYE 2Istanbul University, Cerrahpasa Medical Faculty, Department of Emergency, Cerrahpasa, Istanbul, TÜRKĠYE *[email protected]

The number of criminal cases has been increasing related drugs such as prescribed drugs, legal highs, illicit and new synthetic psychotropic contents.

Aldolan, containing Pethidine HCl, is a synthetic opiate with a phenyl piperidine structure and still have been used as an analgesic especially in severe surgery, amputation and birth pain.

It is known that it has an abuse potential especially in medical staff and patients with a history or tendency of substance abuse, since the drug has been used as a therapeutic agent and easily accessible. The abusers are administered Aldolan continuously with fake complaints and try to provide the drug from different pharmacies even in different cities. It should be investigated whether the related person use the drug for misuse or treatment.

The aim of this study is to determine the pethidine concentration in urine in the case of pethidine abuse.

The concentration of the drug and its metabolites in urine may be important to distinguish between the therapeutic and abused dose. In this study the detection of pethidine in urine sample will be presented with different extraction methods and recovery as extraction efficiency.

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P72. EVALUATION OF DEATH OCCASIONS OCCURRED AT THE RESULT OF POISINING IN ISTANBUL

Murat MERT1*, Alpaslan ÖDEVLĠ2, Hülya YÜKSELOĞLU3, Çetin YEġĠLOVA4 1Forensic Medicine Institution, Istanbul, TÜRKĠYE 2Istanbul Police Headquarters, Public Security Branch Office, Istanbul, TÜRKĠYE 3Istanbul University Institute of Forensic Sciences, Istanbul, TÜRKĠYE 4Yüzüncü Yıl Universtiy, Department of Geology Engineering, TÜRKĠYE *[email protected]

Intoxication occasion occur with the aim of homicide and suicide as well as accidentally. It is important to find out whether the occasion is at the result of homicide, suicide and/or an accident at the death occasions at the result of poisoning as well as the rate of intoxication cases in all death occasions. The reason and the dosage of poisoning at the occassion of poisoning and the specifing of the material causing the poisoning are the area of investigation of the forensic toxicology. In this study, being compared of datas got from it with the other studies carried out the materials used with the aim of poisoning was aimed.

Within this scope, unexpected death, homicide and suicide occasions coming via information centre to Istanbul Police Headquarters, Public Security Branch Office and Homicide Department between the years 2010 and 2014 were analyzed retrospectively. Istanbul is the 23rd most crowded city in the world. Every year, analyzing of average 20-30 thousand occasions is done by crime scene investigation team. One part of these occasions is homicide and suicide and the other part is theft, grab, terrorism and smuggling. 6087 death occasions happened in the first 9 months of 2010 and 2014 were classified as homicide and suicide primarily. Then statistical datas were prepared at poisoning type, dosage and topic of homicide and suicide occasions as being determined the material.

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P73. GOLD NANOPARTICLES INDUCE CYTOTOXICITY: A REVIEW OF IN VITRO AND IN VIVO STUDIES

ġükran ÖZDATLI1*, Feyza KELLECI2, Mohammad CHARESHAZ2, Hande SIPAHI2, Ahmet AYDIN2 1Medipol University, Faculty of Pharmacy, Departmentt of Toxicology, Istanbul, TÜRKĠYE 2Yeditepe University, Faculty of Pharmacy, Departmentt of Toxicology, Istanbul, TÜRKĠYE

Over the last decades, there has been a rapid development in nanotechnology area.These developments lead to promising candidatesfor many biological and biomedical applications which can be used in drug delivery, chemical sensing, biological imaging, and cancer treatment.Nanomaterials are characterized as substances between 1 and 100 nm.In thissense, gold, nickel, carbon, and silverbased nanomaterials are often used in many forms such asspheres, wires, tubes, and rods.Gold nanoparticles (AuNPs) are arising as promising substances from which to establish nanoscale therapeutics and therapeutic delivery systems.As the range of AuNPs,types and their applications continue to improve, there is insufficientinformation on their health effects and no regulatory safety and guidelines relating their properties to toxicities. This review, therefore, focuses on cytotoxicity effect ofAuNPsexperienced so far and their interactions with biological systems. According to literatures, in vivo and in vitro cytotoxicity assays show that the toxicity mechanism of these nanoparticules (NPs) is based on oxidative stress due to free radical formation capacity and cause DNA damage, decrease in cellular growth or apoptosis induction whichare directly associated with physical dimensions like size, shape, coating, concentration, cellular uptake and time.The safety of AuNPsis a subject which receives much attention in recent years. Therefore, for sustainable development of nanotechnology and safety, understanding the effects of AuNPs, characteristics on cellular and biological processes could help in designing AuNPs that are efficient but also nontoxic.

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P74. THE TESTICULAR AND HEPATIC APOPTOTIC EFFECTS OF AROCLOR 1254 IN SELENIUM SUPPLEMENTED AND SELENIUM DEFICIENT RATS

Dilara N. ZEYBEK1, Aylin BALCI2, Ofcan OFLAZ4, Pinar ERKEKOGLU2, Sevtap AYDIN2, Ali ASCI2,3, Ünzile YAMAN2, NurĢen BAġARAN2, Belma KOCER-GÜMÜġEL2* 1Hacettepe University, Faculty of Medicine, Department of Histology and Embryology, 06100 Ankara, TÜRKĠYE 2Hacettepe University, Faculty of Pharmacy, Department of Toxicology, 06100 Ankara, TÜRKĠYE 3Ataturk University, Faculty of Pharmacy, Department of Toxicology, Erzurum, TÜRKĠYE 4Hacettepe University, Faculty of Science, Department of Biology, 06100 Ankara, TÜRKĠYE *[email protected]; [email protected]

The aim of the current study was to determine the apoptotic effect of Aroclor 1254, a polychlorinated biphenyl (PCB), on the testis and liver of selenium supplemented and selenium deficient rats. Selenium deficiency was generated by feeding 3-week old Sprague Dawley rats with 0.05 Se mg/kg diet for 5 weeks. Selenium supplementation group were on 1mg Se/kg diet. Aroclor 1254-treated groups received 10 mg/kg dose by gavage during the last 15 days of feeding period. Apoptotic cell death was determined with terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) assay. The diet with excess selenium did not cause any appreciable alteration in hepatocyte and germ cell apoptosis. Selenium deficiency caused significant enhancement in cell death of both hepatocytes (1.5-fold) and germ cells (2.3-fold). Aroclor 1254 markedly induced apoptosis in rat hepatocytes (2.7-fold) and germ cells (10-fold). Selenium deficiency with Aroclor 1254 treatment was found to aggravate both hepatocyte and germ cell apoptosis while selenium supplementation along with Aroclor 1254 was partially protective. These results put forward the critical role of Se in the modulation hepatocyte and germ cell apoptosis and emphasize the importance of Se status for hepatic and testicular health.

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P75. TRACE ELEMENT STATUS IN LYCOPENE AND/OR OCHRATOXIN A TREATED RATS

S. Sezin PALABIYIK1,2, Murat KIZILGUN3, Pinar ERKEKOGLU1, Gönül ġAHIN4, Belma KOCER-GUMUSEL1* 1Hacettepe University, Faculty of Pharmacy, Department of Toxicology, 06100 Ankara, TÜRKĠYE 2Ataturk University, Faculty of Pharmacy, Department of Toxicology, Erzurum, TÜRKĠYE 3Department of Biochemistry, Diskapi Children‘s Health and Diseases, Hematology, Oncology Training and Research Hospital, 06100 Ankara, TÜRKĠYE 4Eastern Mediterranean University, Faculty of Pharmacy, Department of Toxicology, 10 Mersin, TÜRKĠYE *[email protected]; [email protected]

Ochratoxin A (OTA), one of the most prevalent mycotoxins in the world, has nephrotoxic and hepatotoxic properties. Lycopene is an important carotenoid and has a high singlet-oxygen and free-radical scavenging capacity. This study was designed to investigate the effects of OTA and/or lycopene on the hepatic, renal and testicular trace element status (selenium, zinc and copper) of male Sprague-Dawley rats. Rats (<200 g, n=6) were treated with OTA (0.5 mg/kg/day) and/or lycopene (5 mg/kg/day) by gavage for 7 or 14 days. Hepatic, renal and testicular selenium (20% in liver, 17% in kidney and 40% in testis) and zinc levels (24% in liver, 23% in kidney and 26% in testis) decreased significantly with OTA exposure. Besides, hepatic copper levels decreased markedly in OTA-treated rats. Lycopene supplementation did not affect the trace element levels in any of the organs. Lycopene with OTA treatment provided significant increases in hepatic, renal and testicular selenium and zinc levels. The results of this study showed that at least one of the mechanisms underlying the toxic effects of OTA was its effect on trace element status in different organs, the importance of which needs to be further evaluated. These results also showed that lycopene ameliorated the distribution pattern of essential trace elements in various tissues after OTA exposure.

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P76. MIRTAZAPINE: PHARMACOLOGY, INTER- AND INTRAINDIVIDUAL PHARMACOKINETIC VARIATIONS

Hatice ÖZCAN1*, Emrah DURAL1, H. Sinan SÜZEN2 1Institute of Forensic Sciences, Ankara University, TÜRKĠYE 2Faculty of Pharmacy, Ankara University, TÜRKĠYE

Mirtazapine is the first noradrenergic and specific serotonergic antidepressant. It is an antagonist of presynaptic alpha 2-adrenergic autoreceptors and heteroreceptors on both norepinephrine and serotonin (5-HT) presynaptic axons, plus is a potent antagonist of postsynaptic 5-HT2 and 5-HT3 receptors. The result is increased noradrenergic activity together with specific increased serotonergic activity, especially at 5-HT1A receptors. This mechanism of action maintains equivalent antidepressant efficacy but minimizes many of the adverse effects. Mirtazapine is extensively metabolized in the liver to four metabolites via demethylation and hydroxylation, followed by glucuronide conjugation. Although mirtazapine is a substrate of P450 (CYP) isoenzymes 1A2, 2D6 and 3A4, in vitro studies show that it is not a potent inhibitor or inducer of any of these enzymes. Peak plasma concentration Cmax is reached after about 2 hours. The absolute bioavailability at steady state is approximately 50%. Mirtazapine shows linear pharmacokinetics over a dose range of 15– 75mg/d. Elimination half life of mirtazapine ranges from 20–40 h, and it is dependent on age and gender; females and the elderly show higher plasma concentrations than males and young adults. In a long term therapeutic drug monitoring study results show that, among patients with adverse events, lower desmethylmirtazapine concentrations were observed than in patients with no adverse events. Smoking patients‘ serum concentrations were lower than nonsmokings. Patients on multiple drug treatment had higher dose-corrected mirtazapine and demethylmirtazapine serum concentrations than patients taking only mirtazapine. Large inter- individual variations in plasma mirtazapine and desmethylmirtazapine concentrations have been observed in major depression patients receiving mirtazapine.

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P77. EPIGENETIC CHANGES IN HEAVY METAL CARCINOGENESIS

Serap YALÇIN* Faculty of Engineering and Architecture, Ahi Evran University, Kırsehir, TÜRKĠYE *[email protected]; [email protected]

Heavy metals are harmful to humans include arsenic, cadmium, chromium, lead, mercury, and nickel. Metals can cause significant epigenetic modifications. Epigenetic modifications in chromatin are DNA methylation, covalent modification of cytosine, and post- translational modification of histones, including acetylation, glycosylation, phosphorylation, sumoylation, ubiquitination, microRNAs (miRNA), methylation,and adenosine diphosphate ribosylation. Recent research demonstrates that metal exposure causesmodifications in epigenetic marks, which can lead to relation between heritable changes in gene expression and disease.

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P78. DETERMINATION OF GENE EXPRESSION LEVELS IN CADMIUM CARCINOGENESIS

Serap YALÇIN* Faculty of Engineering and Architecture, Ahi Evran University, Kırsehir, TÜRKĠYE * [email protected]; [email protected]

Cadmium (Cd) is toxic and carcinogenic metalassociated with many diseases. However, the detailed cancer mechanism remains unclear. Researchers have studied to determine gene expression levels in cancer pathway using cancer cells and animal models. The available evidence indicates that Cd changes gene expression levels of metallothioneins, enzymes of glutathione synthesis, heat shock (stress) proteins, zinc transporter proteins, c- fos, c-jun, c-myc, egr-1 etc. Therefore, a possible relationship between gene expression and cadmium may explain for human health risk in further studies.

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P79. MRP1 G1666A GENE POLYMORPHISM IS ASSOCIATED WITH URINE ARSENIC LEVELS

Dilek KAYA-AKYÜZLÜ1, Zeliha KAYAALTI1, Fezile ÖZDEMIR2, Engin TUTKUN3, Tülin SÖYLEMEZOĞLU1 1Ankara University, Institute of Forensic Sciences, Ankara, TÜRKĠYE 2TURKISH REPUBLIC OF NORTHERN CYPRUS 3Department of Occupational Toxicology, Ankara Occupational Diseases Hospital, Ankara, TÜRKĠYE

Multidrug Resistance Protein 1 (MRP1) is a human ATP-Binding Cassette (ABC) transporter protein. It mediates the cellular efflux of various endo- and exobiotics and, thus, protects tissues from toxic insults. MRP1 transports particularly glutathione-, glucuronide- and sulphate-conjugates that are produced by transferases of Phase II enzymes. MRP1 is encoded by ABCC1 gene and polymorphisms can affect the function of this gene and cause inter- individual differences. The aim of this study was to determine the effect of MRP1 G1666A gene polymorphism on urine arsenic levels in 95 Turkish smelter workers. Urine arsenic concentrations were measured by Graphite Furnace Atomic Absorption Spectroscopy (GFAAS) with Zeeman correction and MRP1 G1666A single nucleotide polymorphism was investigated by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. The genotype frequencies were found as 12.6% homozygote typical (GG), 41.1% heterozygote (GA) and 46.3% homozygote atypical (AA). The mean level of arsenic in the urine samples was 5.58±4.37 µg/L. Highly statistically significant association was detected between G1666A polymorphism in the ABCC1 gene (p=0.001). Individuals with the GG genotype had higher urine arsenic level (10.70±7.61 µg/L) than those with GA (4.84±2.54 µg/L) and AA (4.83±3.72 µg/L) genotypes. This study suggested that MRP1 G1666A polymorphism is associated with inter-individual variations in urine arsenic levels.

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P80. TOXICITY of BONSAI

Sinem ÖZCAN, AyĢe KARAKUġ Ankara University, Institute of Forensic Sciences, TÜRKĠYE

Bonsai/Synthetic Marijuana is a derivative of cannabis cannabinoid content in laboratory environment via subtle structural modifications. Recently, not only these new generation psychoactive drugs and its analogues that we face with the modifications in its content and unforeseen rapid increase, show cannabis like effects, but also these may cause various system disorders particularly cardiovascular, gastrointestinal systems and serious acute health problems in brain with its severe side effects such that hospitalization. Comparing the synthetic cannabinoids which are the active substances of bonsai with the classical cannabinoid tetrad tests, it is determined that affinity of cannabinoids, active substances of bonsai, is 4-5 times more than usual and their impact/degradation effect is high as well. For this reason, bonsai cause 100 times more impacts than the impact caused by Δ9-THC (tetrahydrocannabinol) which is major psychoactive component of cannabis. In addition to its declared intoxications, the ones that have been exposed to the negative effects of the substance both can not break their addiction and continue craving drugs. Drug withdrawal symptoms are also observed in regular users. From its first usage to the present, bonsai which is infamous for the increase in death cases caused during the process of exposure (sudden) and its aftermath poses a significant health risk for the community and the magnitude of its toxicity is beyond comparison in proportion to cannabis.

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P81. SLY POISON ARSENIC: OCCUPATIONAL ARSENIC EXPOSURE THAT COME TRUE IN TURKEY

Sabire ÖNEL1, Seren DAYI2 1Ankara University, Institute of Forensic Sciences, TÜRKĠYE 2Gendarmerie Schools Command, TÜRKĠYE

Arsenic belongs to nitrogen group and has three allotropes; which are black, yellow and grey arsenic. Arsenic is 33rd element in the periodic table furthermore, it is colorless and odorless. It can be found in rocks, soil, water and air. There are two forms of arsenic; organic and inorganic. Since inorganic arsenic compounds are more toxic than other compounds, 70- 180 mg of it is enough to kill a human. Arsenic can be exposed through the mouth, skin and air. It accumulates in nails and hair and is excreted via urine, sweat and skin.

Dysphagia, abdominal pain, diarrhea, vomiting, muscle cramps and feeling of dehydration are symptoms of arsenic poisoning. Since arsenic is very poisonous, colorless and odorless, it was used in many suicide and homicide incidents in the past. Many famous people, such as Napoleon, was poisoned by arsenic.

Arsenic poisonings are mostly originated from drinking arsenic contaminated water and being exposed occupationally to arsenic in Turkey. The highest occupational exposure occurred in Kütahya, GümüĢköy so far. Arsenic poisoning causes permanent damage to people, who are exposed to it occupationally, such as cancer, skin lesions and loss of limbs. This study will refer exposure to arsenic occupationally in Turkey.

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P82. FATAL EXPOSURE TO DICHLOROMETHANE IN A PAINT STRIPPER: A PROBLEM OF INDUSTRIAL WORKERS

Erdinç ÖZDEMĠR, Yusuf ÖZER*, Ġbrahim ÜZÜN, Safa ÇELĠK, M. Feyzi ġAHĠN Council of Forensic Medicine, Ministry of Justice, Istanbul, TÜRKĠYE

Solvents are commonly used in paint industry. Dichloromethane (DCM) is frequently used as a solvent both in industrial and household products. It is metabolized to carbon monoxide. Although it does not cause serious harm when it is used in well-ventilated places, it may be life-threatening when used in poorly ventilated enclosed places. It is required that appropriate measures should be taken so that DCM related deaths in workers and consumers can be prevented.

A 44-year old male working in a paint factory was reported to be found dead in a paint cauldron when he had his gloves and mask filtrating air. Physical examination performed revealed an increase in the weight of the lungs due to edema, and congestion on the surface and in the pulmonary sections. Macroscopic and microscopic examinations of the other organs did not indicate any pathological conditions. Toxicological examination revealed DCM in circulatory blood, but normal COHb levels (<5%). The worker was reported to die due to asphyxia caused by inhalation of DCM.

Workers exposed to chemicals should be offered education programs about harmful effects of the chemicals and protective measures regularly. Considering the fact that human life is easily vulnerable, new regulations for the use of solvents should be adopted and put into practice to protect workers‘ health.

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P83. MEDICAL USAGE of ARSENIC TRIOXIDE

Bayram YÜKSEL1*, Arzu EROĞLU1, Nilgün ġEN2 1Ankara Police Forensic Laboratory, Turkish National Police, Ankara, TÜRKĠYE 2Turkish National Police Academy, Institute of Forensic Science, Ankara, TÜRKĠYE

Arsenic compounds have been used for over two thousand years in the treatment of various diseases as a part of the traditional medicine. Anti-leukemic use of arsenic has first been identified at the end of 18th century. It has been used for many years to treat particularly chronic myeloid leukemia and other different kinds of leukemia. Although it is effective, the medical use of arsenic had slowed until 1970s with advent of new chemotherapeutic regimens and radiation therapy. However this situation has changed again after successful reports of arsenic trioxide for acute promyelocytic leukemia (APL) had started to come from China. Inorganic arsenic in the mid-20th century had been used as a therapeutical agent especially in the treathment of leukemia, psoriasis, asthma and chronic bronchitis. The organic arsenic compunds had widely been used in the treatment of protozoal diseases and spirochetal. Nowadays, arsenic trioxide is used in the treathment of acute promyelocytic leukemia (APL). US Food and Drug Administration (FDA) have approved the use of arsenic trioxide for this purpose in 2000.

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P84. ASSESSMENT OF BLOOD-ARSENIC LEVELS OF METALLURGY WORKERS IN TURKEY

Bayram YÜKSEL1*, Zeliha KAYAALTI2, Engin TUTKUN3, Tülin SÖYLEMEZOĞLU2 1Ankara Police Forensic Laboratory, Turkish National Police, Ankara, TÜRKĠYE 2Ankara University, Institute of Forensic Science, Ankara, TÜRKĠYE 3Department of Occupational Toxicology, Ankara Occupational Diseases Hospital, Ankara, TÜRKĠYE

Arsenic exposure in humans has been associated with development of adverse health effects such as neurologic and cardiovascular effects, diabetes mellitus, skin lesions, skin, lung, kidney and liver cancers. Occupatational exposure to arsenic usually occurs with inhalation of arsenic-containing particles in mining industry. A simple and sensitive method was developed and validated to determine the arsenic levels in the biological samples by Graphite Furnace Atomic Absorption Spectrometry (GFAAS) equipped with Zeeman background correction system. Blood, urine and hair samples are known to be the best biomarkers to assess arsenic exposure in humans. Samples were collected from 95 metal workers who admitted to Ankara Occupational Diseases Hospital in Turkey. Prior to analysis; the samples were pre-treated with the acid digestion procedure. The method showed linearity in the range of 0-100 µg/L with a detection and quantification limit equal to 0.37 µg/L and 1.1 µg/L respectively. The calibration curve was characterized by a high correlation coefficient (r2=0.9983). Validation of the method was performed in terms of repeatability and accuracy with the use of reference materials. The evaluated arsenic levels of blood samples in metallurgy workers ranged between 3.83 and 52.44 µg/L in. Mean arsenic levels in blood of silver metal workers are found as 21.25±12.47 µg/L.

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P85. TOXICOLOGY OF SYNTHETIC CANNABINOIDS AND THEIR ANALYSIS IN HERBAL MATERIALS

Bayram YÜKSEL1*, Arzu EROĞLU1, Zeliha KAYAALTI2, Nilgün ġEN3, Taner BORA1 1Ankara Police Forensic Laboratory, Turkish National Police, Ankara, TÜRKĠYE 2Ankara University, Institute of Forensic Science, Ankara, TÜRKĠYE 3Turkish National Police Academy, Ankara, TÜRKĠYE

The existance of herbal abused drugs in the market is not a new problem. Such materials generally consist of plant mixtures with little psychoactive effects. However, the composition of these herbal products has changed into new pyschoactive compounds known as synthetic cannabinoids. Synthetic cannabinoids has taken place in recreational drug use all around the world including Turkey. These substances which have very similar effect to marijuana are globally produced in clandestine laboratories to place on the market. Undesired harmful effect profiles of synthetic cannabinoids have not been studied in humans yet, however there are very limited researches in animals. For this reason, most of knowledge related to their toxicity comes from hospital emergency services and treatment reports obtained in forensic case studies. In recent years, synthetic cannabinoids have gained a great attention of forensic sciences. Compounds having the most insterest to forensic scientist can be typed as JWH, CP, HU, AM, WIN, RCS and recently XLR and UR. Research due to mechanism of cannabis activity has started when molecules with similar structure to Δ9-tetrahydrocannabinol (THC) which is the main psychoactive ingredient of marijuana were first examined. A synthetic analogue of THC, ‗HU-210‘, was first synthesized in Israel in 1988. Though these substances are firstly synthesized for medical research, recently they take place in illicit drug market. The solution of the compounds concerned are dissolved in organic solvents and sprayed onto herbal materials. The goal of this study is to interpret toxicology of synthetic cannabinoids. It is also aimed to offer an identification method using Gas Chromatography-Mass Spectroscopy (GC-MS) for synthetic cannabinoids in herbal products caught by law enforcement.

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P86. METAL TOXICITY IN AGRICULTURE

Esma SÖYLEMEZ1 1Middle Black Sea Passage Generation of Agricultural Research Station Director, Tokat, TÜRKĠYE

Soil is being polluted by heavy metal accumulation, exponential industrial aresas, fertilizers used on agricultural lands, pesticides; and on the other hand sewage mud, coal combustion wastes, leaded gasoline and paint. Heavy metals are ranked among the most destructive soil pollutants. Lead (Pb), chrome (Cr), arsenic (As), zinc (Zn), cadmium (Cd), mercury (Hg) and nickel (Ni) often occur in contaminated soil which are among hazardous chemicals. One of these heavy metal ions; Cd is an important soil pollutant. Heavy metal accumulation in agricultural lands is closely related to soil characteristics. Especially pH of the soil, amount, cation transition capacity are the most important soil characteristics which effect heavy metal behaviours and convection to the plant in clay mineral type soil. Convection of heavy metals to animals and humans by agricultural production, and related to this accumulation concentration in enverioment, animals and humans are effected by physical, chemical and biological characteristics of soil. Heavy metals in the soil block physiological activities of plants, decrease productivities and cause their death. At the same time they cause decrement of crop quality and quantities. On the other hand residues on the crops cause economical loss by effecting exportation. Heavy metal pollution in the soil may be harmful for human and ecosystem by contacting polluted soil, food chain (soil –plant – human or soil– plant–animal–human), and polluted groundwater. Type of amount of heavy metal is effective in accumulation of heavy metals in human body. Toxic heavy metals cause biological activity disorders, consequently various deseases even plenty of cancer varieties.

Toxical effects of high degree heavy metals which are being used for different purposes in Turkey agricultural lands on soil, water, agricultural crops and human health will be discussed in this compilation.

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P87. FATAL POISONING OF CHILDHOOD IN TRABZON (TURKEY)

Hulya KARADENIZ1, Ismail BIRINCIOGLU2,3, Ozgur TURNA1, Huseyin Cetin KETENCI1, Nazım Ercument BEYHUN4 1Trabzon Branch of the Council of Forensic Medicine, TÜRKĠYE 2Karadeniz Technical University, Medical Faculty, Forensic Medicine Department, TÜRKĠYE 3Karadeniz Technical University, Forensic Science Institute, TÜRKĠYE 4Karadeniz Technical University, Medical Faculty, Public Health Department, TÜRKĠYE

The aim of this study was to expose the characteristics of medicolegal children autopsies of childhood poisonings in Trabzon (Turkey), from 2009-2013, in order to contribute to the available data on this topic. The cases were analyzed according to the following criteria: age groups, sex, toxic substance category and origin. Children were divided into four age groups: 0-5 yr, 6-9 yr, 10-13 yr, and 14-18 yr. Major toxic substances were classified in five categories as: carbon monoxide, insecticides, drugs, mushroom and snake venom. The most common cause of fatal poisoning in children was carbon monoxide (64.5%, n=40), followed by drugs (16.1%, n=10), insecticides (9.7%, n=6), mushroom (6.5%, n=4), and snake venom (3.2%, n=2). Age range was 0 to 18 years (9.10±5.77). The Statistical Package for Social Sciences (SPSS) version 13 was used in data analysis.

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P88. NANOTECHNOLOGY IN FORENSIC SCIENCES

Zehra TOPAL1*, Dilek KAYA-AKYÜZLÜ2 1Gazi University, Department of Chemical Engineering, Ankara, TÜRKĠYE 2Ankara University, Institute of Forensic Sciences, Ankara, TÜRKĠYE *[email protected]

In this century, the scientists denominate nanotechnology as industrial revolution because of its possibilities offered. Nanotechnology means understanding, controlling and being made functional of substances whose dimensions are 1-100 nm. In 1959, Richad Feynman talk about nanotechnological materials that was shown in Science Fiction movies very time ago in his talk entitled ―There is Plenty of Room at the Bottom‖. The term ―nanotechnology‖ was used by Taniguchi in 1974. Nanotechnology germinating with microscopes that can scan at nano-dimension made a quick introduction to our lives with several products which are not to be contaminated, not permeable to UV lights, do not require ironing, have anti-aging properties, can clean themselves etc. Nanotechnology draw attention in science world since substances show different properties in nano dimension and makro dimension, which is very remarkable. For instance, substances that not react with any other substances in the normal conditions can be reactive in nanodimensions. In forensic sciences, nanotechnology is used for analyizing the hair, tail, tissue and organ samples with nano microscope (TEM, SEM, AEM, STM). Some of these mentioned microscopes are able to manipulate atoms and image surface tomography. Nanotechnology that is in the early stages of development can be used different areas of science with vision of scientist. Recently, fingerprint imager‘s sprey are developed by using nanoparticles in our country. In this study, nanotechnology entering our life very fast and its usage in forensic sciences will be discussed in the light of literature.

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P89. SALBUTAMOL POISONING INDUCED HYPOKALEMIA: A CASE REPORT

Selahattin ARTUÇ1, Kamil Hakan DOĞAN1, Seyyit KUġ2 1Selcuk University Faculty of Medicine Department of Forensic Medicine, Konya, TÜRKĠYE 2Dicle University Faculty of Medicine Department of Biochemistry, Diyarbakır, TÜRKĠYE

Although poisonings are in all age groups, in the pediatric age group has remained more common and more deadly. 80% of poisoning cases are children under 5 years of age. Poisonings with substances from the gastrointestinal tract are seen the most common poisonings (%75).

Salbutamol is a beta-2 adrenergic agonist, although it is a drug used in the treatment of bronchial asthma, also is recommended for use in serious heart failure, congestive cardiomyopathy and early pregnancy. Typical side effects observed in case of overdose are; agitation, tremor, tachycardia, hypotension, hyperglycemia and hypokalemia.

Ten-year-old girl admitted to Selcuk University Faculty of Medicine Department of Forensic Medicine with her medical documents that sent in order to prepare forensic report. After examining the medical documents and obtaining history from her mother, it was understood that she was brought to the emergency department with flutter complaint by her mother. She took Ventolin syrup (150 ml, salbutamol sulphate, 2 mg / 5 ml) which was prescribed by her doctor with a diagnosis of bronchitis but she did not know the amount of it. When examined on admission, her conscious was clear, her fever was 37º degrees, pulse 140/min, blood pressure of 100/60 mmHg. Sinus tachycardia was detected in ECG. In biochemical screening; potassium (K) was 3.1 meq/L (reference: 3.5 to 5.1 mEq/L), sodium (Na) was 134 mEq/L (reference: 136 to 145 mEq/L). Potassium supplementation was performed. The symptoms such as tachycardia and hypokalemia were considered symptoms due to beta-2 adrenergic agonist toxicity.

The main reason of poisoning is consumption of medicine by children accidentally or due to the carelessness of the families. Parents should be educated about preventing access to any kind of medicine of children.

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P90. PLASMA CONCENTRATIONS OF IMATINIB AND N-DESMETHYL IMATINIB IN CHRONIC MYELOID LEUKEMIA PATIENTS

Pelin KILIÇ1*, Zeliha KAYAALTI1, Mehmet GÜNDÜZ2, Günhan GÜRMAN2, Tülin SÖYLEMEZOĞLU1 1Ankara University Forensic Sciences Institute, Ankara, TÜRKĠYE 2Ankara University School of Medicine Department of Hematology, Ankara, TÜRKĠYE

Chronic myeloid leukemia (CML) is a serious myeloproliferative cancer. Imatinib is the first line treatment. Imatinib's primary metabolism depends on the presence of cytocrome P450 (CYP450) enzymes. The active metabolite is N-desmethyl imatinib (norimatinib). Pharmacologic effects of imatinib and norimatinib are similar. Norimatinib can accumulate in the plasma 10-30% of imatinib. The aim of this study was to analyze certain parameters which maintain their importance in clarifying imatinib's pharmacologic effects. To investigate plasma concentrations, 41 CML patients (18 women, 23 men) on 400 mg oral imatinib treatment at Ankara University School of Medicine Hematology Department in Turkey were included. Mean age and mean treatment period were 46.97 and 4.29 years, respectively. Pharmacokinetic analysis of imatinib and norimatinib was performed by liquid chromatograhy tandem mass spectometry (LC-MS/MS). LOQ values for imatinib and norimatinib were 66 ppb and 62.5 ppb, respectively, whereas LOD values were 30 ppb and 25 ppb, respectively. Recovery of imatinib and norimatinib were recorded as 98.45% and 92.47%, respectively. Average plasma imatinib-norimatinib levels were 4 ppm and 1 ppm, respectively. Sigmoidal 2-tailed Pearson correlation test revealed significant correlation between concentrations of the two compounds. However, individual norimatinib/imatinib percentages suggested intraidividual variability to drug response (min. value 7.917%, max. value 58.72%). Statistical results are in line with scientific knowledge already established for imatinib and its pharmacokinetics. Nevertheless, individual results have shown that pharmacologic effects of imatinib may differentiate among patients. Further studies related to individual characteristics and environmental factors are necessary to enlighten intraindividual differences of imatinib behavior.

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P91. IS IT GOOD, BAD OR UGLY? WHICH ONE IS TRUE? Mehmet TOSUN1 1Ankara University, Forensic Sciences Institute and Abant Izzet Baysal University, School of Medicine, Department of Medical Biochemistry, TÜRKĠYE

Monosodium glutamate (MSG) is sodium salt of the common amino acid glutamic acid

(Molecular formula is C5H8NNaO4). It may be naturally occur in many foods like tomatoes, potatoes and dairy products. In food industry, it is used a food additives (E621) to give savory taste (flavor enhancer). MSG is produced in laboratory by the fermentation of some carbohydrate based products like molasses. MSG is added in many foods like chips, biscuits and canned vegetables. U.S. Food and Drug Administration (FDA) accepts the addition of MSG to foods to be ―generally recognized as safe‖ (GRAS). However the use of MSG remains controversial in many countries. For this reason these countries including FDA require that it be listed on the food label. Up to date it was reported MSG may be related with some symptoms known as MSG symptom complex which includes headache, flushing, sweating, chest pain and nausea. However, scientist have reported that no definitive evidence of a link between MSG and these symptoms. Because of glutamate is one of the most important neurotransmitter in human brain, research of the possible side effect of the MSG has focused on this side. Some data indicate that MSG may be related with the sperm concentration reduction in male and MSG-treated rats are more susceptible to develop depressive-like behaviors. Also it has shown that MSG treatment in the rat enhances hippocampus β-amyloid accumulation important in neurodegenerative disorders including Alzheimer's disease.

In conclusion, human toxicologist should take role to investigate the proof of the relations between MSG and these findings. Answer of the title seems that MSG is ugly.

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P92. HOW DID THEY POISON ME?

Duygu YAVUZ, Jale Nur DĠNÇ, Kübra ġEKER*, UlaĢ SAĞDUYU, Halide Nihal AÇIKGÖZ Ankara University, Forensic Sciences Institute, Ankara, TÜRKĠYE *[email protected]

Forensic entomotoxicology tries to enlighten into cases of death, where a death occurs due to drug or toxins, through the analysis of the insects. Entomotoxicological data is used to support the evidence where an available tissue cannot be found for such analysis. These analyses are conducted with the larvae, pupae and the adults of thearthropod family specieses such as the Muscidae, Calliphoridae andthe Staphylinidae. The purpose of this study is to examine toxicological analysis of the insects which belong to the cases that involves deaths by poisoning. Forensic entomological analysis related articles have been searched and examined.

Toxicologic analysis of the homogenized insects helps us to identify and to quantify the toxic substance(s) within death cases that involves substance abuse and other kinds of toxicity This will give us valuable data regarding to the death. Through this data, the time of death, child abuses, suicides, drug abuses and neglect cases can be processed.

The recovery of the entomological evidence from the bodies involved in medicine and narcotics related death cases, the entomotoxicologicaldata willassists the case. Forensic entomotoxicology is new for our country and further researches should beconducted.

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P93. A REVIEW ON THE TOXICITY OF NSAID’S FAMILY DRUGS

M. ġAHINER1, B.A. TÜYLÜ2 1Bilecik ġeyh Edebali University, TÜRKĠYE 2Anadolu University, Faculty of Science, Department of Biology, EskiĢehir, TÜRKĠYE

Among numerous drugs being developed so far, pain killers take the lead in terms of human consumption frequency. Pain killers are analgesics used for the main purpose of suppressing pain by affecting both the peripheric and the central nervous system. It‘s known that the excessive use of pain killers lead to significant diminish in suppression of pain, along with severe damage to the stomach, kidneys and to the liver. Generally, pain killers are opioid drugs, non opioid synthetic drugs, and non-steroidal anti-inflammotary drugs (NSAID). NSAIDs are analgesic, antipyretic and anti-inflammotary efficient drugs. Most if not all of them are competent in treating pain, rash, oedema and heat rashes. This treatment consists the non spesific inhibition of the cyclooxygenase (COX-2) enzyme. Dexketoprofens are, along with being a member of the NSAID family, originate from the derivations between profens. They are frequently used as active ingredients in pain killers. Dexketoprofens have been the core element of numerous in vitro studies so far, with the aim of treating certain discomforts along with the aim of specifying the pain threshold. In addition, the active ingredient in studies of this drug has been shown to be cytotoxic. Some studies show that Ketoprofen‘s 1.5- 5 mg/kg ¹ doses in the range in vultures‘s kidney and 5-10 mg/kg doses in the range in birds‘ liver caused toxic effects. Also in vivo studies on rats demonstrate that 36.9 mg/ml dose was a significant cytotoxic effect.

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P94. THE EVALUATION OF CYTOTOXIC EFFECTS OF SUPPLEMENTARY GLUTAMINE CONSUMPTION IN HYPERICIN-MEDIATED PHOTO DYNAMIC THERAPY IN COLON CANCER CELLS

Aysun KILIÇ SÜLOĞLU*, Elif KARACAOĞLU, Güldeniz SELMANOĞLU Hacettepe University, Faculty of Science, Department of Biology, Beytepe, ANKARA

Glutamine is a crucial amino acid in gluconeogenesis, protein and nucleic acid synthesis and also in cancer metabolism. Glutamine can be produced in sufficient quantities under stable conditions, but under metabolic stresses becomes a limiting amino acid and make the organism vulnerable to infections. A number of studies showed that exogenous glutamine can support the gut glutamine metabolism after chemotherapy, radiation, injury and other catabolic states. But the reports about usage of glutamine supplements while photodynamic therapy in colon cancer are rare.

In this study, Caco-2 colon adenocarcinoma cells were incubated with 0.1 µMand 0.25 µM hypericin containing DMEM, after 24 h medium was changed with glutamine-free (Group I), 4 mMglutamine (Group II) and 20 mMglutamine (Group III) containing low-dose glucose DMEM. Then the cells were irradiated with 4 J/cm-2. 24 h after hypericin activation cell cytotoxicity were measured by MTT assay.

According to the results, cytotoxicity increased depending on the hypericin concentration when compared to control group. On the other hand, the cytotoxic effects of hypericin decreased depending on the glutamine concentration. In 4 mM and 20 mM glutamine groups, cell viability started to increase again reflecting the decrease in efficiency of phytotherapy.

In literature, the effect of glutamine supplementation and oncology are conflicting, in vitro studies reveal an increase in cellular growth with glutamine supplementation which is supporting our results.The usefulness of glutamine uptake may change according to the tumor size, cell type, treatment method and patient.

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P95. VINCLOZOLIN EXPOSURE DURING PREGNANCY IN WISTAR RATS: EVALUATION OF TOXICITY ON FETAL BONE DEVELOPMENT AND FETAL LIVER

Elif KARACAOĞLU1*, Aysun KILIÇ SÜLOĞLU1, Evrim Arzu KOÇKAYA2, Güldeniz SELMANOĞLU1 1Hacettepe University, Faculty of Science, Department ofBiology, 06800, Beytepe, Ankara, TÜRKĠYE 2The Higher Vocational School of Health Services, Gazi University, 06830, GölbaĢı Campus, Ankara, TÜRKĠYE

Vinclozolin is a chlorinated fungucide which is used predominantly for protecting fruits and vegetables against various fungal pathogens by inhibiting spore germination. It is used in foods crops such as grapes, ornamentals, turf grass (threating all human), fruits and vegetables in greenhouses (threating greenhouse workers). It has been recently indicated that vinclozolin may act as antiandrogenic effect in in vivodue to antagonist affects of androgen receptors of its metabolites M1 ve M2.

In this study, 50 mg/kg/bw and 100 mg/kg/bw vinclozolin in corn oil were administered orally to pregnant rats during gestation. At the end of the study, fetal liver were observed histochemically and immunohistochemically. Additionally, skeletons offetus were examined morphologically. According to results, increased number of magekaryocyte, cellular degeneration and congestion were observed in fetal liver. VEGF immonostaining of fetal liver were denser in treatment groups. Furthermore fetal skeleton morphology had minor changes in response to vinclozolin treatment during gestation.

As a result of the study, vinclozolin exposure during pregnancy had toxic affects on fetal liver and also it had minor affects on fetal skeleton morphology.

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P96. DO THE NEEDLES USED FOR ACUPUNCTURE HAVE TOXIC EFFECTS? ‘HEAVY METAL DEPOSITION IN THE SKIN; ARGYRIA’

Bilge GEÇĠOĞLU1, Ersel GEÇĠOĞLU2, S.SETENAY MĠT2 1Ankara University, Institute of Forensic Sciences, TÜRKĠYE 2Gazi University, Traditional and Complementary Medicine Center, TÜRKĠYE

Argyria is a condition characterised by bluish-grey to slate-grey staining of the skin and mucous membranes caused by deposition of silver particles in the skin, secondary to acute high level, or to chronic lower level, exposure to elemental silver, silver dust or silver compounds.

Forms of localisedargyria are the appearance of blue macules at sites of acupuncture needles and silver earring sites, ocular argyrosis from overuseof silver containing eyedrops or cosmetic makeup.

FDA approvedacupunctureneedles as medicalsuppliesIn 1996.Modern acupuncture needles are in various lengths and width. The metals used for acupuncture needles are silver, gold, cupper and stainless steel. There is a few argyria cases reported due to silver needles used for acupuncture.

World Health Organisationsays;‗Stainless steel is the material of choice for acupuncture needles. Each should be carefully checked before use. If it is bent, the shaft eroded, or the tip hooked orblunt, the needle is defective and should be discarded.‘ and ‗Acupuncture can be considered inherently safe in the hands of well trained practitioners.‘

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P97. LEAD POISINING RELATED TO GUNSHOT WOUND

Ekin ÖZCAN Ankara University, Forensic Sciences Institute, Ankara, TÜRKĠYE

Although they are rare cases, lead poisoning due to guns hot injuries have to be treated since they can cause various complications. Initial symptoms can appear in a wide time intervals that can change between two days to 52 years after the injury. Exposure to lead may lead to neurotoxicity and some disorders in the reproduction, circulation and endocrinal systems of humans and animals. Especially the interaction of synovial and spinal fluids with the lead, since this will cause the lead to dissolution, accelerates the toxical effect. It is thought that thelevel of lead solubilization changes depending on the surface area exposed to the lead, position of the bullet and the length of time it stayed in the body. This uncertainty makes the diagnosis of the toxicity even more difficult. This is why in gunshot injuries, to be able to prevent the level of lead in the blood from increasing, chelation therapy must be applied to remove the heavy metals from the bloodstream. It is thought that applying this therapy before the surgical operation can reduce the risk of lead poisining. The aim of this study is to present some recent cases and researches related to lead poisoning due to gunshot injuries.

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P98. CASE REPORT: DEATH FOLLOWING SYNTHETIC CANNABOID ABUSE

Volkan ZEYBEK¹*, Tuba YAMAN², Kemalettin ACAR², Özgür DEMĠRKAN¹, Semih PETEKKAYA³ ¹Council of Forensic Medicine, Denizli, TÜRKĠYE ²Department of Forensic Medicine, Pamukkale University Medical Faculty, Denizli, TÜRKĠYE ³Council of Forensic Medicine, Malatya, TÜRKĠYE

Synthetic cannabinoids are increasingly used in Turkey as marijuana substitutes. However, reports of severe toxicity, resulting from their use, are limited. We present the case of death following synthetic cannabinoid inhalation with antemortem hospital records, autopsy findings, postmortem histopatologic and toxicologic analyses results.

A 20-year-old man with no significant medical history presented at the emergency department with loss of consciousness and hyperthermia. He had smoked a synthetic cannabinoid product called "bonsai", had drunk alcohol and took some drugs prior to the onset of symptoms. Physical examination showed heart arrythmic and tachycardic, decreased breath sounds, body temprature 40,7 °C, then intubated. Laboratory evaluation, blood pH 6,9, ethanol 30,3 mg/dl, troponin I >50000. CK-MB >1000. Cardiac arrest became, CPR began and he was dead. Postmortem examination, we saw subepicardial hemorrhagic area at left ventricule and hemorrhagic areas at apex in myocardial sections. Histopatologic findings, there was focal bleeding between subendocardial myocardial fibers. Toxicologic findings, analysis of blood by LC/MS procedure confirmed presence of JWH-018 and MDA (methylelendioxyamphetamine), internal organ samples by GC/MS procedure showed presebce of DDE (diphenyldicloroethylen).

Synthetic cannabinoids are legal in many parts of the world and easily obtained over the Internet. Data on human toxicity are limited and real-time confirmatory testing is unavailable to clinicians. Clinicians, lawmakers, and the general public need to be aware of the potential toxicity associated with synthetic cannabinoid use.

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P99. STEVENS-JOHNSON SYNDROME AFTER USED LAMOTIRIGIN AS A MALPRACTICE CASE SUBJECT

Berna DURMUġ, Ümit Naci GÜNDOĞMUġ, Habib BOSTAN Council of Forensic Medicine, TÜRKĠYE

The Stevens-Johnson syndrome is a serious mucocutaneous vesiculobullous disease that begins acutely and limits itself generally. It may develop by the use of several routinely used drugs. That's why the physicians who prescribe such drugs may be sued for malpractice. In our case, the Stevens-Johnson syndrome that has developed as a result of Lamotrigine use and become a matter in dispute will be examined from a medicolegal perspective.

The patient is a 52-year-old lady who had been followed up in the physician's private practice for four years due to major depression diagnosis. After her latest control, 100 mg lamotrigine has started to be administered at 2 doses a day: in the morning and in the evening. In spite of being called for a control, the patient skips this control, and at the 40th day of administration she applies to hospital complaining about eruption, rash and bulge on her skin. Her drug use is stopped, the antihistamine and steroid treatment is started, and the patient is sent back to home. At the night of the same day, she applies to a university hospital complaining about the same symptoms again. She is diagnosed to have Stevens-Johnson syndrome based on findings such as eruption, rash, bulge, inability to open eyes, and high Ig E.

Such manifestations caused by drug hypersensitivity reaction appear before us as malpractice cases in forensic practices. While examining such a drug toxicity manifestation from the malpractice perspective, we think that it is necessary to consider whether the prescribing physician has informed the patient about the side effects, whether he was able to know the reaction manifestation emerging during the treatment process, and whether he has taken the necessary actions for treatment of the emerging manifestation.

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P100. ACUTE TOXIC EFFECTS OF DELTAMETHRIN ON NARROW CLAWED CRAYFISH (AstacusleptodactylusEsch. 1823)

Çağlan Karasu BENLĠ1*, Göktuğ GÜL2 1Gazi University, Instituteof Natural and Applied Sciences, Department of Environmental Sciences, Ankara, TÜRKĠYE 2Gazi Üniversitesi, Health Services Vocational School, Department of Environmental Health, Ankara, TÜRKĠYE *[email protected]

In the present study, deltamethrin, a synthetic pyrethroid, contaminating aquatic ecosystems, will be investigated for determination of acute toxic efffects on narrow clawed cray fish (AstacusleptodactylusEsch. 1823). Crayfish of 24.16 ± 4.12 g mean weight and 10.28 ± 0.76 cm mean length were selected for the bioassay experiments. The experiments were repeated three times, in 10 L tap water. Water temperature was 21 ± 1 °C. The data obtained were statistically evaluated by the use of the E.P.A computer program based on Finney‘s probit analysis method and the 48 and 72 h LC50 values for crayfish was calculated to be 0.326 (0.149-0.683) and 0.269 (0.121-0.636) µg/L, respectively in semi static bioassay test system. Behavioral changes of crayfish were recorded for all concentrations. In conclusion, deltamethrin is very highly toxic to crayfish, a non-target organism in the ecosystem.

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P101. ACUTE TOXICITY OF SYNTHETIC PYRETROID PESTICIDE IMIPROTHRIN ON GUPPY (Poeciliareticulata)

Göktuğ GÜL1, Emre USTA2, Çağlan Karasu BENLĠ3 1 Gazi University, Health Services Vocational School, Department of Environmental Health, Ankara, TÜRKĠYE 2Ministry of Environment and Urban Planning, Ankara, TÜRKĠYE 3Gazi University, Instituteof Natural and Applied Sciences, Department of Environmental Sciences, Ankara, TÜRKĠYE *[email protected]

In the present study, imiprothrin, a synthetic pyrethroid pesticide contaminating aquatic ecosystems as a result of agricultural facilities and human health issues can be reached. Through rain and drainwater was investigated acute toxic effect on Guppy (Poeciliareticulata). Experiments were conducted in two stages as range finding test and main test. In each experiment, five different imiprothrin concentrations and two control groups have been used. The experiment has been carried out with static bioassay method on three series during 96 h. Datas were evaluated using the U.S. E.P.A. LC50 computer program based on Finney‘s Probit Analysis Method. During the main tests, the behavioral changes of guppy in each concentration were observed. In addition, macroscobic signs were also evaluated after exposure to imiprothrin. According to bioassay results 24, 48, 72 and 96 h LC50 (95% confidencelimits) values for guppy exposed to imiprothrin were 225.95 (193.60-269.57) µg/L, 214.44 (184.20-248.39) µg/L, 179.60 (149.61-208.90) µg/L, 174.34 (143.61- 203.92) µg/L, respectively. It has been observed that, contrary to control group, guppy exposed to different concentrations of imiprothrin were swimmed upside down, crowded at the water surface of the aquarium, some of them moved rapidly or slowly before death, and showed abnormal swimming. Afterdeath, somefish had swollen abdomen and hemorrhage at th ebase of the fins.

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P102. EFFECT OF CHRONIC ARSENIC EXPOSURE AND GLUT1 POLYMORPHISM IN THE DEVELOPMENT OF DIABETES MELLITUS

Dilek KAYA-AKYÜZLÜ1, Fezile ÖZDEMĠR2, Zeliha KAYAALTI1 1Ankara University, Institute of Forensic Sciences, Ankara, TÜRKĠYE 2TURKISH REPUBLIC OF NORTHERN CYPRUS

Human can exposed to arsenic via drinking water, soil resources, air and nowadays mainly by occupationally. Arsenic is classified as a Group I carcinogen by International Agency for Research on Cancer (IARC). Chronic exposure to arsenic can cause to cardiovascular diseases, diabetes mellitus (DM), dysfunction in neural system or many diseases. In the world and also Türkiye, the number of patients having DM has been increasing every days and there have been many researches on why, how and what can lead to the development of DM. As a consequence of these studies, it is suggested that some of the single nucleotide polymorphism (SNP) which is located in Glucose transporter 1 (Glut1) gene region can be associated with DM. In this review, the SNPs which are related with chronic arsenic exposure and DM, and which SNPs can be researched in Turkish population will be mentioned in the light of previous studies.

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P103. WELDER’S LUNG DISEASE: CASE REPORT

Nur ġafak ALICI1, Türkan Nadir ÖZĠġ1*, Ġbrahim Onur ALICI2, Engin TUTKUN1, Hınç YILMAZ1 1Ankara Occupational Disease Hospital Ankara, TÜRKĠYE 2Ankara High Specialty Hospital Training and Research Hospital, TÜRKĠYE

Welding is the joining process with different materials in a certain temperature and pressure. Welder persons can expose to several metals and mineral dusts, particularly molten iron powder smoke during welding process. Welder‘s lung disease is an occupational illness, which is caused by different factors within welding fumes, affects the respiratory tracts in all levels, and is a mixed inhaled exposure disease in both airways and parenchyma.

Forty-seven-year-old male patient admitted to hospital with exertional dyspnea and dry cough within 2 years. He smokes a pocket of cigarette per day for 30 years. He reported that he has used all kinds of welder sources, mainly electrical. On physical examination, it is noted that arteriel tension: 135/85mmHg, pulse: 85/min., SpO2: 94%, respiratory rate 18 breaths/min. Respiratory sounds were bilaterally normal. Laboratory investigations showed that acute phases of patient were within normal limits. Respiratory function test (RFT) showed FVC:93%, FEV1:92%, FEV1/FVC:81% and FEF25-75:77%. In a PA lung graphy, there are a few nodular opacities in both lungs. High Resolution Computed Tomography (HRCT) of the lungs demonstrated ground-glass density nodules and patch areas of ground-glass opacities mainly in upper zones of the both lungs. The diagnosis was Welders‘ lung disease and the patient has been followed clinically and radiologically.

Welder‘s lung disease is a preventable occupational disease. Although, protection is the main principle in the prevention from disease, individuals with occupational risk for the development of this disease should be followed.

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P104. SILICOSIS WITH FOUR CASES

Türkan Nadir ÖZIġ1*, Nur ġafak ALICI1, Ġbrahim Onur ALICI2, Dilek ERGÜN1, Engin TUTKUN1, Hınç YILMAZ1 1Ankara Occupational Disease Hospital Ankara, TÜRKĠYE 2Ankara High Specialty Hospital Training and Research Hospital, TÜRKĠYE

Silicosis is parenchymal lung disease that is caused by inhalation of silica dusts in the crystal structure and thus resulting in fibrosis. Exposure to silica particles can cause silicosis in miners, quarry workers, sandblasters, glass-makers, foundry and ceramic workers, and construction workers involved in highways, tunnels and cement. In the present study, 4 male ceramic workers whose ages are 26, 37, 43 and 45 years will be presented. In their routine examination, lung graphies demonstrated pathological evidences. They work in the same workplaces in 10, 15, 17, 23 years, respectively. Three of them have smoking habit. On physical examination, respiratory sounds were normal. In the lung graphies of cases, bilateral millimetric nodules were seen, and large opacity according to ILO calcification system was detected in one case. High Resolution Computed Tomography (HRCT) of the lungs demonstrated diffuse micronodular interstitial involvement that is concentrated in the upper lobes of both lungs. In respiratory function test, small airway obstruction was detected in one case. Respiratory function test and diffusion capacities were normal in other 3 cases. Silicosis was diagnosed in these patients and they have been followed clinically and radiologically.

Silicosis is a preventable occupational lung disease. After diagnosis, cessation of exposure is important in the progression of the disease. Ceramics workers who work under dust control measures are also significant in the prevention of silicosis disease.

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P105. COLLECTING, PACKAGING AND TRANSFERRING THE TOXICOLOGICAL EVIDENCE IN CRIME SCENE

Ersin KARAPAZARLIOGLU1*, Murat MERT2 1Faculty of Security Sciences, Turkish National Police Academy, Ankara, TÜRKĠYE 2Ankara Regional Center of The Council of Forensic Medicine, Ankara, TÜRKĠYE *[email protected]

There are lots of evidence in crime scene in forensic cases. In these evidences, one of the evidence groups which have special importance is toxicological evidence. It should be demonstrated maximum sensitivity in searching, finding, collecting and transferring the toxicological evidence in crime scene. These are very important to health of crime scene investigator and security of evidence.

Narcotic drugs (materials for preparing the substances with drugs), drugs, toxicant, gases, body fluid and samples (blood, urine, vomit and hair) belongs to toxicological evidence group in a crime scene. It is implemented different research, collection and transfer method for every types of evidence. The experts collecting the evidence in crime scene must firstly take the protective measures for himself (galosh, mask, glove and protective suit) and then collect the toxicological evidence with proper equipment. After packaging these collected evidence with proper wrapping material must be transfer to laboratory as soon as possible.

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P106. TARGETED GENE THERAPY OF CANCER: IMMUNOTOXINS

Mehmet Kadir ERDOĞAN Department of Biology, Faculty of Arts and Sciences, Bingöl University, Bingöl, TÜRKĠYE [email protected]

Cancer is one of the most common devastating diseases and the second leading cause of death in humans. To develop a novel anti-cancer therapy, there has been an intense research on various biological sources. Most chemotherapeutic agents and surgery have some limitations and all of conventional therapies show the need for novel therapy, with a wider margin for safety and good selective toxicity to the tumor. Biologic therapy, proton therapy and photodynamic therapy are new modes of targeted therapies, selectively aimed at cancerous tissue, so minimizing toxicity and enhancing potency.

Immunotoxins are proteins that contain a toxin conjugated to an antibody or growth factor by genetic fusion or by chemical ligation, can potentially provide a more effective and specific treatment for cancer than other contemporary methods. Protein toxins that are used in cancer treatment along with targeting molecules are plant toxins (such as ricin, abrin, saporin, gelonin), bacterial toxins (such as diphtheria toxin, pseudomonas exotoxin), fungal toxins (such as restrictocin) and animal toxins (e.g. hemolytic toxin from sea anemone). Monoclonal antibodies, immunoglobulins, cytokines, and growth factors are the immune system components which have been used as targeting molecules.

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P107. HAS THE SPECIMEN BEEN PRESERVED CORRECTLY FOR THE MEASUREMENT OF ETHANOL?

Nurgul OZCAN, Alpaslan OZTURK, Fatma UÇAR, Fatih DOGAN, Ali YALÇINDAĞ, Ismail TEMEL DıĢkapı Yıldırım Beyazıt Training and Research Hospital, Department of Clinical Biochemistry, Ankara, TÜRKĠYE

Ethanol is the most frequently encountered toxic substance in both clinical and forensic analytical settings.Ethanol is used to treat methanol poisoning and prophylactically to prevent the occurrence of alcohol withdrawal symptoms.Clinical laboratories therefore need rapid and reliable methods for detection and quantitation of ethanol in biological fluids, usually plasma/serum and urine.

Specimens should be collected into fluoride oxalate to inhibit glycolysis and prevent generation of ethanol by certain bacteria or yeasts within the specimen.However fluoride oxalate is unsuitable for many clinical tests and preservation is considered unnecessary.Contamination by microorganisms may also result in false obvious increases in ethanol concentration. Specimens must be kept well stoppered and preferably refrigerated to prevent loss of ethanol.The use of alcohol-containing swabs to clean the venipuncture site has generally been discouraged, but in a study has been reported that alcohol swabs led to minimal interference as measured by GC.Specimens with increased lactate and lactate dehydrogenase concentrations can give falsely increased ethanol results with some enzymatic assays.Anticoagulants don‘t interfere with the enzymatic or GC procedures.Some hospital regulations require that ethanol analysis be performed on unclotted samples.In a study has been reported that analysis following homogenization of the clot produced results comparable to those obtained with unclotted specimens.It has been shown that sealed samples of whole blood or whole blood plus fluoride can be stored at 0°C to 3°C or at room temperature (22°C to 29°C) without significant loss of ethanol content over a 14-day period.

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P108. THE NAME OF DANGER IN UNDERGROUND MINING: CARBON MONOXIDE POISONING

E. INCESU1, T. HANCI 2* 1Konya SeydiĢehir Government Hospital, TÜRKĠYE 2DıĢkapı Yıldırım Beyazıt Training and Research Hospital, TÜRKĠYE *[email protected]

Mine accidents in our country, as all over the world, constitutes a significant part of industrial accidents. The mining industry is the most difficult and risky line of work due to its particular nature, and the fact that it contains a large number of interconnected risks which trigger each other as a chaining in case of any adverse events. So, in order to minimize these risks, a large knowledge, experience, expertise and continuous monitoring is required. Carbon monoxide poisoning occurred due to explosion of firedamp (methane gas + air mixture) takes place at the top of the occupational accidents from which suffer the employees of this line of work.

Carbon monoxide is an extremely poisonous, colorless, odorless and flammable gas. Due to the fact that the ability of Carbon monoxide to combine with hemoglobin is 200 times more than the ability of oxygen, hemoglobin combines with carbon monoxide instead of oxygen and creates carboxy-hemoglobin when such gas is found in the environment. Carboxyhemoglobin (COHb) causes the reduction of the oxygen amount transported to the tissues. The organs most affected by hypoxia are the organs having the most metabolic activity.

This study is made in order to contribute to the studies about carbon monoxide poisoning they experienced in underground mining and accidents occurring in mining sector and for the prevention of these accidents.

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P109. TOXICOLOGICAL FINDINGS IN BONES

Fulya YÜKSEL, Arsen ASLANOĞLU Ankara University, Institute of Forensic Sciences, Ankara, TÜRKĠYE

Poison is a substance that gives harm to cells and living tissues chemically, biochemically or radioactively. Toxicology which is the study of poison, studies the origin, features of the poison, the effects that it has on organisms, treatment against it and its toxic dosages. Poisons do various kinds of harm to systems inside organisms and bones are one of them. Bones are the hardest tissue that makes up the body. While having a suppporting role bones are also the calsium storage of the body and there are 206 bones in an adult. There are osteocyte, osteoblast, osteoclast, inter cellular fluid matrix in the bone tissue and composes of 7 different parts. These are periosteum, compact bone, spongy bone, red bone marrow, yellow bone marrow, blood vessels and articular cartilage.

Since prehistoric ages different kind of diseases have been diagnosed by bones. Heavy metals, radioactive elements, halogenes, nonmetals and volatile organic compounds damage the bone in various ways. Lead, cadmium, aluminum, strontium and mercury are heavy metals that cause chronic poisoning that lead to weakness in bones, osteoporosis, osteomalacia, demineralization, spinal deformation, growth retardation, bone tumors and leucemia. Radium, uranium and plutonium that are radioactive elements can cause decalcification and softening in bone, skeleton deformation and bone tumors. Also fluorine a halogene damages the calsium metabolism and causes osteoporosis and osteosclerosis; nonmetal phosphorus degenerates the bottom jaw and bones. While having storage role for some elements, bones are also like a shelter that a lot of toxic substances hold on to and accumulate.

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P110. SNAKE VENOM TOXINS: MECHANISMS OF ACTION

Arzu EROĞLU1, Bayram YÜKSEL1, Berrin Imge ERGÜDER2 1Ankara Police Forensic Laboratory, Turkish National Police, Ankara, TÜRKĠYE 2Ankara University, Faculty of Medicine, TÜRKĠYE

Snake venoms are mixture of enzymes and non-enzymatic proteins. They are highly modified saliva containing zootoxins which facilitates the immobilization and digestion of prey. In general, snake venom is a yellowish, whitish or colorless liquid. It is little sticky and slightly heavier than water. Structure of snake venom is decayed whether it is left to open air. Snake venom remains effective for long years provided that it is stored in a dark and cool place. Dried poison can be solved in pure or salt water (1% NaCl is sufficient). Poison is taken into a glass vessel by a sort of milking. The most ideal method for this is to let the snake bites a beaker which is surrounded by parafilm or membrane. Generally, the mechanism of action occurs in two ways: hemolytic and / or neurotoxic. Hemolytic poisons causes bleeding and disintegrating in tissues (especially vipers and rattlesnakes). Neurotoxic poisons have effect on the nervous system (especially cobras, coral snakes, sea snakes and some colubrid). At present, it is known that some types of snakes have both neurotoxic and hemolytic effects. However, some snake venom toxins have great potential as medicine for treating diseases. In this review, we interpret the mechanism of action for snake venom toxins on human tissue.

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P111. CARBON MONOXIDE (CO) POISONING

Arzu EROĞLU1, Bayram YÜKSEL1, Berrin Imge ERGÜDER2 1Ankara Police Forensic Laboratory, Turkish National Police, Ankara, TÜRKĠYE 2Ankara University, Faculty of Medicine, TÜRKĠYE

Carbon monoxide (CO) is a colorless, odourless and tasteless gas that is slightly less dense than air. It is formed in the process of incomplete combustion of organic substances, including fuels. CO intoxication is one of the most common types of poisoning all around the world. We are all exposed to small levels of carbon monoxide throughout the day. CO poisoning can frequently be observed in mines or a fire as well as burning carbon containing fuels in places with low ventilation and depending on exhaust smoke in garage or similar places. When carbon monoxide is inhaled, it is immediately and largely absorbed into blood and distributed throughout the body. The distribution of carbon monoxide in the body extensively reflects the binding of carbon monoxide to heme proteins (e.g., Hb, myoglobin). CO binds to hemoglobin existing in the red blood cells approximately 200 times faster than oxygen. Combination of carbon monoxide and hemoglobin results with a new product named as carboxyhemoglobin (COHb). Oxygen in our body is replaced by carbon monoxide as oxygen concentration decreases. Blood can not carry enough oxygen to the tissues. Heart, brain and other organs becomes inactive. The most common symptoms of carbon monoxide poisoning may resemble other types of poisonings such as headache, nausea, vomiting, dizziness, fatigue, and weakness. Neurological signs include confusion, disorientation, visual disturbance, syncope and seizures.

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P112. EVALUATION OF THE ETHANOL LEVEL BY DEMOGRAPHIC CHARACTERISTICS OF PATIENTS

Alpaslan OZTURK, Nurgul OZCAN, Tuba HANCI, Zeynep YILDIZ, Fatma UCAR, Gonul ERDEN Diskapi Yildirim Beyazit Training and Researching Hospital, Biochemistry Laboratory, TÜRKĠYE

Ethanol is one of the most commonly abused toxic substances. Ethanol suppresses central nervous system. We aimed to investigate distribution of ethanol analysis in our hospital by age, sex, month and ethanol level.

Electronic database was searched between November 2013 and October 2014 retrospectively. 4249 patients (768 women, 3481 men) which were requested ethanol assay were enrolled in the study. Serum Ethanol was measured with Siemens ADVIA 1800 chemistry autoanalyzer.

In 1548 patients (36.4%) ethanol levels were detected >10 mg/dL (accepted positivity). 1216(78.6%) and 332(21.4%) of these patients were male and female respectively. Ethanol concentrations were 10-20 mg/dL, 20-50 mg/dL and >50 mg/dL in 26, 86 and 1104 of male patients, respectively. Ethanol concentrations were 10-20 mg/dL, 20-50 mg/dL and >50 mg/dL in 8, 14 and 310 of female patients, respectively. The age range of male patients ethanol detected were 0-18 (n=48, 4%), 19-25 (n=201, 16.5%) and over 25 years (n=967, 79.5%). The age range of female patients ethanol detected were 0-18 (n=34, 10.2%), 19-25 (n=49, 14.8%) and over 25 years (n=249, 75%). Among males, the highest mean level of ethanol was 213 mg/dL in April and the lowest mean was 160 mg/dL in August. Among females, the highest mean level of ethanol was 232 mg/dL in March and the lowest mean was 152 mg/dL in December.

Although male gender had a higher rate of accepted positivity for ethanol, mean ethanol levels in females were higher.In individuals under age 18, ethanol positivity were more frequent in females.

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P113. ENTOMOTOXICOLOGY IN FORENSIC SCIENCES: CURRENT APPROACHES

Hüseyin ÇAKAN1, Filiz Ekim ÇEVĠK1, Türker Togay AKSOY2 1Ġstanbul University, Forensic Medicine Institute, TÜRKĠYE 2Ġstanbul Aydın University, Biomedical Device Technologies, TÜRKĠYE

In Forensic Sciences, entomotoxicology is a new branch compared to entomology. In the researches concerning the active substances leading to death, when tissue and biological liquid samples cannot be found, bone marrow and hair tissues, and when they cannot be obtained, Diptera and the other Arthropods are reliable alternative materials for toxicologic analysis. Entotoxicology examines the toxicologic analysis application of the necrophagous bugs, for the purpose of establishing the toxins found in the tissues after drugs and intoxication. Moreover, it is also assessed to assist PMI (proportional mortality indicator) estimations. In view of the definition and verification of the toxic substance that resulted in death particularly in death due to heroine and cocaine abuse and drug intake in cases of accident or suicide, interest in this branch has increased in forensic medicine. Bugs easily homogenize and can be easily analyzed with general toxicological analysis procedures. To determine the drugs in the bugs, in general gas chromatography-mass spectrometry (GC / MS) and liquid chromatography-mass spectrometry (LC / MS) are used. As an alternative method, for establishing the metabolic footprint of the bugs (lipids, proteins etc.), near infrared spectroscopy (NIRS), which is a fast and more cost-effective method, is used. In this reseach, examples of entomotoxicological studies are given and it is aimed to examine the issue with the new alternative methods.

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P114. RELATIONSHIPS BETWEEN GENETIC POLYMORPHISM AND DRUG: FORENSIC PHARMACOGENETIC

Filiz Ekim ÇEVĠK1, Yasin Hasan BALCIOĞLU1, ġükriye KARADAYI2, Hüseyin ÇAKAN1 1Ġstanbul University, Forensic Medicine Institute, TÜRKĠYE 2Ġstanbul University, Public Health Directorate, TÜRKĠYE

Forensic pharmacology is a multidisciplinary field, where pharmacology and law intersect, which requires obtaining knowledge in not only in pharmacology, but also in he legal aspects, which therefore covers a wide area and where a different knowledge is required. Forensic pharmacology requires synthesizing with law knowledge and using pharmacology knowledge including pharmacokinetics, pharmacodynamics, toxicology, antemortem and postmortem drug/substance analyses etc. Pharmacokinetics and pharmacodynamics of the drug taken differ due to the genetic differences of the people. When pharmacokinetics changes, course of the drug within the body changes. This genetic difference in the enzymes playing role in elimination and/or metabolism of the drug is important. Thus, when these enzymes are much, the drug will be metabolized rapidly and if the concerned drug is not prodrug, then its period of effect or effect will reduce. This way, differences among the persons having the same drug will arise. Or in the contrary case, if the enzyme amount is less, then the drug will remain at the toxic level and as it will be eliminated late in the body, undesired effects will arise. Thus, although a person gets recovered after admitting the drug, it will have a toxic effect on another person. Purpose of this study is to evaluate the relationship between genetic polymorphism and drug and to refer to the recent studies in this field.

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P115. SYNTHETIC CANNABINOIDS: BONZAI

Vecdet ÖZ1, Filiz Ekim ÇEVĠK1, AyĢe KAYA1, Hüseyin ÇAKAN1 Ġstanbul University, Forensic Medicine Institute, TÜRKĠYE

Synthetic cannabinoids are substances with similar chemical structural effects to the active substance of marijuana, which is Δ9-tetrahidrokannabinoid (THC). Their receptors bearing similar characteristics with THC affect the brain and the other organs. After discovery of Δ9- tetrahydrocannabinoid (Δ9-THC) isolation in 1964 and cannabinoid receptors (CB1 and CB2) in 1980s, numerous cannabinoid receptor agonists were produced for theurapatic purposes. On the other hand, cannabis has become the illegal substance that is produced and consumed the most in the world. Since 1997, over 200 psychoactive substances have been defined. In 1990s, compounds with cannabinoid receptor activity that are known as ―JWH substances‖ were synthesized and in time, these substances have become the main component of the new substances that contain synthetic cannabinoid (SC). Since 2004, SCs have not only been available in the market, but also become popular among those looking for legal fuddling substances. Substances containing SC are generally called ―Spice‖ in Europe and ―Bonzai‖ in Turkey. Because of the common use of these substances, of which structures are not known completely in terms of dosage and content, and of the lack of specific regulations, increasing consumption of SCs as the designed and abused substances has become a serious problem for public health institutions. Upon SCs sales on the Internet and shops called ―head shop‖ and their being offered as herbal incense sticks, fuddling effect occurring upon having these herbal mixtures has become to be discussed on the Internet and particularly in the substance forums, and this accelerated popularity of SCs. And with our research, we aim to touch upon the current developments in this issue and its mechanism.

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P116. BIOCHEMICAL AND HISTOPATHOLOGICAL EFFECTS OF IN UTERO EXPOSURE DI-N-HEXYL PHTHALATE AND DICYCLOHEXYL PHTHALATE IN PREPUBERTAL, PUBERTAL AND ADULT STAGES OF WISTAR FEMALE AND MALE ALBINO RATS

Müfide AYDOĞAN AHBAB, Nurhayat BARLAS, Gözde KARABULUT* Hacettepe University, Science Faculty, Department of Biology, Ankara, TÜRKĠYE

Effects of maternal di-n-hexyl phthalate and dicyclohexyl phthalate exposure to rats at various doses were investigated during developmental stages. Pregnant rats were treated by gavage application on gestational days 6-19. The groups were classified as follows: control, vehicle control (corn oil), 20, 100, 500 mg/kg/day DHP and 20, 100 and 500 mg/kg/day DCHP. Female and male pups were classified for developmental stages as prepubertal, pubertal and adult. End of the study, hematological and biochemical parameters in serum were determined. In addition, weights of liver, kidney, spleen, lung, brain, heart, stomach and thymus were measured organ/body weight ratios were calculated and tissue sections examined histologically.

In toxicological tests, low and high treatment doses (20 and 500 mg/kg/day) of DHP and DCHP caused a significant increase of granulocyte and lymphocyte percent. In prepubertal and pubertal rats, hematocrit value of the 500 mg/kg/day DCHP groups were increased but, in adult rats were decreased compared with the controls. In all DHP treatment groups AST, ALT and LDH serum levels were increased significantly. In histopathological examinations, especially, high dose of DHP and DCHP treatment group, some histopathological findings were observed in liver, kidney, spleen and lung tissue.

This study showed that DHP and DCHP had significant effects in female and male rats during developmental stages.

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P117. THE ROLE OF CYP ENZYMES IN DRUG METABOLISM

Hasan ÇOBANKAYA Hacettepe University, Ankara, TÜRKĠYE

Drug metabolism, has become a major pharmacological science with particular relevance to toxicology. Among the major enzyme systems affecting drug metabolism, cytochrome P450 enzymes are dominant. The cytochrome P450 enzymes, abbreviated CYPs (for cytochrome Ps), are a very large group of enzymes that belongs to heme-coupled monooxygenases and catalyze drug, xenobiotic and endogenous compound oxidations, playing a key role in deactivation, activation, detoxification and toxification of most drugs.

The CYPs are encoded by the CYP gene superfamily and there are 12 gene families of functionally related proteins comprising this group of enzymes. So far more than 55 CYP genes have been described in the human genome and these are classified in families and subfamilies. Their naming and classification relate to their degree of amino acid sequence homology. CYPs are found not only in liver but also in the gastrointestinal tract, lung, kidney, skin, placenta, prostate, and other tissues.

CYP enzymes are responsible for metabolism of more than 80% of all commonly prescribed and over-the-counter medications. Since most of the CYP enzyme isoforms are polymorphic in nature, ethnic and inter-individual genetic differences may greatly affect the metabolism of some clinically important drugs. These differences may cause therapeutic failure, adverse drug reactions or even toxicity and death. In case of such drug toxicity events forensic toxicological approaches may be of great value for evaluating the possibilities.

In this study various isoforms of CYP enzymes will be reviewed, common mechanisms of CYP-mediated reactions will be explained and clinically important drug substrates of CYP enzymes will be listed. The factors that influence activity of various CYP enzymes will also be reviewed in this study.

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P118. EVALUATION OF OCCUPATIONAL AND HOME ACCIDENTS CAUSED BY SULPHURIC ACID: TWO CASE REPORTS

Fatmagül ASLAN1, Zerrin ERKOL1,2, Serdar TĠMUR1, Zafer DAĞLAR3 1Antalya Education and Research Hospital, Forensic Medicine Unit, Antalya, TÜRKĠYE 2Abant Izzet Baysal University, Faculty of Medicine, Forensic Medicine Department, Bolu, TÜRKĠYE 3Antalya Education and Research Hospital, Child Surgery Clinic, Antalya, TÜRKĠYE

Sulfuric acid; with the formula H2SO4 is a powerful and highly corrosive chemical. It can corrode many different materials up to living tissues, metals and stones. This compound has a broad range of applications from plungers up to lead acid batteries. It is known as ―battery acid‖ among the public. It transmits electric. Very high heat is produced when it is dissolved in water. It has also an important role in many industrial applications such as fertilizer production, petroleum refining, wastewater treatment, and chemical synthesis, dyestuff and explosives. However, it can be extremely irritating and dangerous. If swallowed or inhaled it can cause serious burns to the respiratory tract. In addition, it may cause severe burns in case of contact with skin or eyes. Area in contact with the acid should be washed with eye shower or diluted base. Heat will be released if washed with water and this event will perform the main combustion. In this study it is intended to present two accident originated sulfuric acid burn cases and draw attention to measures that can be taken to prevent these types of accidents. Case 1: From examining the legal and medical documents; it was understood that a 36-year-old male worker doing sink and kitchen cleaning at the day of the event, stated that he used a dust mask and dishwashing gloves during the application, but he has not taken any measures to protect the eye area, and his face and eyes were exposed to sulfuric acid steam during cleaning and partially to sulfuric acid itself which splashed directly to the face. In the examination of the patient in a private hospital he was taken to; intense edema in both eyelidFs and inflammation in the eye, skin erosion in the facial area and eyelids, intense epithelial damage in cornea and conjunctiva were detected. Eye and face shower with 0.9% NaCl was performed. He was taken under observation for three days, and discharged after medication. Case 2: In the examination of judicial documents; it is determined that a 10 kg sulfuric acid in a plastik canister which was bought for cleaning the log and delivered to the doorman was set out to open space in the garden, that the canister had no warning letter on it. That the hands dirty children decided to wash their hands with the content of the canister, and that the 5 years old girl who poured the acid in her hands was taken to the hospital immediately because of the chemical skin burns. Blisters and severe painful red areas with widespread 2nd degree burns in both hands, wrists and palms were detected in the examination held in hospital. The patient was hospitalized in the pediatric surgery service and was discharged after medical treatment with medical follow- up recommendations. The presented cases illustrates the importance of working with this type of abrasive chemicals in fume cupboards or in well ventilated areas, the use of protective clothing and goggles while working, and preservation of these substances in containers made of dark glass or in non reactive canisters labeled as irritant and corrosive substances in places not easy to access.

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P119. DRUG USE IN DEMENTIA PATIENTS

Hayri ERKOL1, Fatmagül ASLAN2, Zerrin ERKOL2,3, Serdar TĠMUR2 1Abant Izzet Baysal University, Faculty of Medicine, General Surgery Department, Bolu, TÜRKĠYE 2Antalya Education and Research Hospital, Forensic Medicine Unit, Antalya, TÜRKĠYE 3Abant Izzet Baysal University, Faculty of Medicine, Forensic Medicine Department, Bolu, TÜRKĠYE

Dementia is a disease in which the brain demonstrates inability to maintain daily life issues, knowledge and behavior and often arises over the age of 50. It is mostly associated with symptoms such as weakness of memory and attention in person, inability of name recalling, word finding and naming objects, path finding, calculation, communication and social skills, to perceive matters in issue. Albeit slowly it usually follows progressive course. Demantia may be due to Alzheimer's disease, chronic cerebrovascular disease, alcohol, infection, etc. In the further period of the disease people may lose their time, location and person orientation. These patients may not know where they are, may not recognise people close to them, and sometimes even close family members.

One of the most important problems in patients with dementia due to developing forgetfulness is the issue about forgetting taking drugs. People can remain drug-free for forgetting to take medication, therefore primarily forgetting the use of drugs for the treatment of dementia itself, and any necessary drug for any disease, may eliminate the chance of treatment of these diseases. Or vice versa, these people may forget that they have taken drugs and take the drugs over and over again, this behavior can lead to overdose table. Both conditions may lead to serious complications that can occur in people's death.

In this study; it is intended to mention the problems of dementia patients experienced in different stages of the disease since the beginning and draw attention to possible solutions.

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P120. SAFETY BEGINS AT HOME: CHILDHOOD POISONING IN TURKEY

Merve ĠYRAS, Emine Firdevs YILDIRIM Ankara University, Institute of Forensic Sciences, Ankara, TÜRKĠYE

Poisoning, intake or exposure to any kind of substances (poison) that can damage vital functions‘of body. Access or uses of a substance by wrong person, in the wrong way, and in the wrong amount are main cause of poisoning in all around the world. When poisoning cases are analyzed 49% of the cases have seenin childhood (0-6 years) in Turkey. Frequency of childhood poisoning is 0.9% of the all emergency cases.

Most of the childhood poisoning happens at home result of an accident in Turkey. When childhood accidents in home is investigated and ranked poisoning comes in third after fall/slip and burning. Cleaning supplies, medicines and pesticides are top three of the source of childhood poisoning.

In this study, our aim is attract attention to ever-increasing childhood poisoning cases and suggest proposals for prevention.

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P121. A REVIEW OF THE PERSPECTIVES ON SYNTHETIC CANNABINOIDS, RECEPTORS AND ACUTE EFFECTS

Merve PARLAKGÖRÜR1,2, Nilgün ġEN1, Taner BORA2, Bayram YÜKSEL2, ÇağdaĢ AKSOY3 1Turkish National Police Academy, Institute of Forensic Sciences, Ankara, TÜRKĠYE 2Ankara Police Forensic Laboratory, Turkish National Police, GölbaĢı, Ankara, TÜRKĠYE 3Diyarbakır Police Forensic Laboratory, Turkish National Police, Diyarbakır, TÜRKĠYE

The present review highlights overall to the worldwide, there has been an increasing demand and availibility in novel psychoactive drugs, known as synthetic cannabinoids (SC). It has been a growing consumption especially among younger generations since at least 2010. The endocannabinoid system (ES) includes two types of cannabinoid receptors; the CB1 and CB2. The most probable acute effects are impaired central nervous system, cardiovascular disease avd adolescent psychosocial development and mental health. Up to now, these new drugs are commonly available for sold on the internet in many countries and fastly changing formulations and changing brand names, therefore these samples make a huge complexity in blood and urine detection. The findings observed in the clinic, as well as the central nervous system, cardiovascular system, adversely affect vital functions such as respiratory and digestive system. Such as, difficult breathing, heart rhythm disorders, coughing, nausea and anxiety level as to cause serious concluded that the increase is quite effective compared to other drugs. Long term synthetic cannabinoids use can be damaged brain cells and central nervous system.

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P122. ROLES OF CHELATION IN HEAVY METAL DETOXIFICATION

Yasemin KARTAL*, Tülin SÖYLEMEZOĞLU Ankara University, Institute of Forensic Sciences, TÜRKĠYE *[email protected]

Metals serve as essential components play critical roles not only biochemical but also physiological functions in the system. On the other side, heavy metals can cause serious toxic effects. Chelation therapy is used for this heavy metal toxicity. By this means, further metal absorption into the system is prevented and metal is eliminated from the circulation. An ideal chelator should have greater affinity, low toxicity and same distribution as the metal. In addition it should have high water solubility and should eliminate rapidly toxic metal. Chelation therapy is very effective against to acute poisoning and it removes metals from soft tissues. In other respects oral therapy is available and it has ease application. In spite of that, most chelators have adverse effects. For example; essential metal can loss, poor clinical recovery, non-specific binding, metal from intracellular sites can't be removed. Nevertheless it is very important to determine the need for more specific. Moreover, newer strategies should be investigated for better treatment. Such as combination therapy with lipophilic and a hydrophilic chelator, investigate roles of chelation in natural toxicokinetics may improve the therapeutic results.

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P123. COMPARISON OF TOXICITY OF CRIME SCENE EQUIPMENT

Behice ġeyda TÜREDĠ1, Niyazi Umut AKINCIOĞLU2, Gürcan PARACIKLI3 1Ankara Provincial Directorate of Security 2Ankara University, Institute of Forensic Sciences 3Ministry of Health Public Health Agency of Turkey

Crime scene investigation used in biological, chemical and physical tests evaluate the toxic properties of the equipment and to compare the toxicity of the equipment

Scene of blood, hair, saliva, nasal discharge, sweat, semen, urine, vaginal-rectal swab, tissue samples, bone, teeth, nails, feces, dandruff, skin rashes, fingerprints, footprints, such as rutting and narcotics chemical, toxic aimed to compare the terms of the instruments used during the determination of physical and biological evidence and the collection and identification of measures to be taken. In all, luminol, phenolphthalein, ninhydrin, leucocrystal violet, fingerprint powders, CPB, iodine vapor, dizafluero, silver nitrate, physical developer, superglue, MTN, diaminobenzidine, DMAC, MMD, RTX (ruthenium tetroxic), gas chromatography, atomic absorption spectroscopy, X-ray analyzer is an scanning electron microscope, such as the test methods examined can be measured toxicity can be created by these methods, or create and then to determine the subject of the study was to determine whether the method can be used as an alternative to these methods.

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P124. ANALYSIS OF PHTHALATES ESTERS IN HUMAN BIOLOGICAL SAMPLES

Emrah DURAL, Zeliha KAYAALTI Ankara University, Institute of Forensic Sciences, TÜRKĠYE

Phthalates are high-production chemicals commonly used in plastic products and are used in many household and personal care products, toys, and medical supplies, as well as in plastics to improve flexibility. The ubiquitous use of phthalates results in widespread human exposure. Exposure to phthalates has been associated with altered hormone levels, reproductive effects (male fertility), precocious puberty in pubertal girls, increased incidence of chronic disease, and a possible role in the development of cancer. Upon exposure, humans rapidly metabolize phthalate diesters to the corresponding monocarboxylic acid derivatives, the hydrolytic phthalate monoesters, which depends on the phthalate diester that may be oxidized. The hydrolytic phthalate monoesters may be the bioactive species. All these phthalate metabolites are excreted in the urine and feces in their free or glucuronidated forms. Various analytical methods have been developed for measuring phthalate monoester metabolites separately in biological materials (Feces, Urine, Plasma, Sweat, Milk, Placenta, and Amniotic Fluid). Mostly using gas chromatography coupled with mass spectrometry (GC–MS) and liquid chromatography coupled with mass spectrometry (LC–MS) or tandem MS (LC–MS/MS). LC–MS/MS methods, which combine high selectivity and sensitivity, show an advantage over GC–MS methods because of simple sample preparation without the need for derivatization. Due to the increasing concern on the endocrine disrupting chemicals, such as phthalate esters, and the needs to assess their exposure to individuals, it is essential to have a sensitive, low cost and efficient analytical method that can quantify these chemicals or their metabolite levels simultaneously in human biological materials.

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P125. SILDENAFIL: TOXICITY AND ANALYSIS METHODS

Emrah DURAL1*, Gülseren KARABIYIKOĞLU2, Tülin SÖYLEMEZOĞLU1 1Institute of Forensic Sciences, Ankara University, TÜRKĠYE 2Department of Chest Diseases, Faculty of Medicine, Ankara University, TÜRKĠYE

Sildenafil citrate (1-[4-ethoxy-3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo-[4,3- d]pyrimidin-5-yl) phenylsulphonyl]-4-methylpiperazine) is widely prescribed for the treatment of pulmonary arterial hypertension (PAH) and impotence-male erectile dysfunction. Sildenafil citrate is a potent and selective inhibitor of cyclic guanosine monophosphate specific PDE5, and causes relaxation of smooth muscle, in particular, in the pulmonary vasculature and corpus cavernosum. Oral sildenafil is absorbed rapidly, reaching peak plasma concentrations after ≈1 hour. It is metabolized principally by cytochrome P450 (CYP) 3A4 and to a lesser extent by CYP2C9, and inducers or inhibitors of these isozymes can affect the clearance of sildenafil. Sildenafil is predominantly excreted as metabolites in the feces (≈80% of the administered oral dose), with ≈%13 excreted in the urine, and has a terminal elimination half-life of 3–5 hours. Sildenafil undergoes first-pass metabolism and the mean absolute bio- availability is ≈%41. The major (N-desmethyl) metabolite of sildenafil has an in vitro potency approximately half that of the parent compound. Because of its increasing popularity and potential side effects, the need for a procedure to detect both sildenafil and N- desmethyl sildenafil in biological samples is becoming increasingly important. Several high- performance liquid chromatographic (HPLC) methods have been reported for the determination of sildenafil and/or N-desmethyl sildenafil in biological samples. Gas chromatography–mass spectrometry (GC/MS), micellar electrokinetic chromatography, liquid chromatography–mass spectrometry (LC/MS) as well as liquid chromatography–tandem mass spectrometry (LC/MS/MS) methods have been reported.

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P126. BONZAI IS NOT NATURAL, IS THE CHEMICAL. KILL!

F. OZTURK1*, E. Altay OZTURK2, E. COSKUNSU3 1Ankara University, Institute of Forensic Sciences, Ankara, TÜRKĠYE 2Gazi University, Graduate School of Natural and Applied Sciences, Ankara, TÜRKĠYE 3Ankara University, Institute of Forensic Sciences, Ankara, TÜRKĠYE *[email protected]

Recently, according to research in the areas of forensic science, new psychoactive substances, particularly synthetic cannabinoids, in Turkey and other countries have revealed serious problems. This new generation psychoactive substances defined in two different ways. Firstly, these substances have come out by some substances which are used in various fields and mentioned in scientific literature being used out of their functions. The other definition, these substances have came out as a result of changes being done in molecular level existing substances going beyond legal restrictions. In general, substances containing synthetic cannabioid are called as "spice" in Europe "K2" in America and "bonzai" in Turkey. The use of bonzai is similar to marijuana. Thus synthetic cannabinoids are solved in a suitable solvent such as ethyl alcohol or acetone. Solution is sprayed on plant natural leaves that absorbent plant leaves and then the mix is left to dry again for evaporation of the solvent. Unnatural psychoactive substances are injected into the natural plant leaves. So bonzai is thought natural products. Furthermore it has been presented to the market, as a natural product. Also, this situation happens a commercial deception. In this study, we focused on which bonzai is not a natural substance; it is actually a unnaturel substance. We aimed to show toxic defects of these substances. Finally this study aimed to creat awarness to people.

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P127. DRUGS RELATED SUICIDES IN UNITED KINGDOM

Pinar TARGAN1, Esra BALCIOGLU2, Zeliha KAYAALTI2 1British Transport Police, Scientific Support Unit, London UK 2Ankara University, Forensic Science Institute, TÜRKĠYE

Drug overdose is a common lethal method of suicide in the world (67%). The rapid rise in freely availability of the drugs to buy legally from shops throughout the UK has become a risk factor for suicide. Drug poisoning deaths involve a broad spectrum of substances, including legal and illegal drugs, prescription drugs (either prescribed or obtained by other means) and over-the-counter medications. Drugs most commonly used in overdose were (in order) heroin/morphine, amphetamines, paracetamol (and related compounds), benzodiazepines (diazepam), anti-depressants, SSRI and opiates. A total of 2.995 numbers of cases of drug- related deaths registered in 2013 in the UK, 2.032 male - 923 female deaths. Male drug misuse deaths (including illegal drugs) increased by 23%, from 1.177 in 2012 to 1.444 in 2013. Female drug misuse deaths increased by 12%, from 459 in 2012 to 513 in 2013. 56% of all deaths related to drug poisoning in 2013 were involved an overdose of opiates. Deaths caused by due to use of legal high increased by 15%, from 52 deaths in 2012 to 60 deaths in 2013. Present data indeed showed that antidepressants were identified in almost a quarter of suicidal victims. Therefore, drug misuse between accidental and deliberately self-harming deaths may confirm the possibility of depression as a risk factor for suicide. Antidepressants have been frequently reported as a major means of self-poisoning [>39 years of age]. The use of paracetamol and related compounds were also reported as most commonly consumed drug and identified in intentional death victims, with its use for suicidal purposes being a well- known phenomenon in the UK. Drug overdose in suicide is common in United Kingdom due to easily availability of the drugs. Drug users should be educated on the risk factors associated with overdose.

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P128. THE MOST WIDELY USED SYNTHETIC CANNABINOIDS IN RECENT YEARS

Esra BALCIOGLU1, Pinar TARGAN2 1Ankara University, Forensic Science Institute, TÜRKĠYE 2British Transport Police, Scientific Support Unit, London UK

In recent years, there has been an increase in use of synthetic cannabinoids. New synthetic cannabinoids are added to existing ones day by day and new synthetic cannabinoids are released to the market named as Spice, Bonsai, K2, Dream, Incense, Green Giant and etc. Moreover, it is also difficult to detect synthetic cannabinoids in routine toxicological testing. In this case, it causes some difficulties to define synthetic cannabinoids and to cope with them. Some expressions such as ‗incense‘, ‗not for human consumption‘ or ‗natural‘ are used on packages offered for sale in order to hide the real contents. Synthetic cannabinoids real THC made sales (tetrahydracannabinol) in the laboratory to create the effect of synthesized JWH-018 (1-pentyl-3-(1-naphthoyl) indole) is formed by spraying with chemicals, such as plant leaves. Their usage in serious high heart rate (120-150), anxiety attacks, high blood pressure, can cause irreversible toxic effects and even death. In this study, it has been examined the types of synthetic cannabinoids‘, routes, the reasons that make vendors and why users choose synthetic cannabinoid, toxic effects on humans, the using situation of USA, UK and in some EU countries. According to the data obtained available on UK, USA, Australia, Netherland, New Zealand, Germany, Portugal, Hungary, Turkey and etc. were found to be used in other countries. The countries that identified substances banned synthetic cannabinoids in the years of 2008, 2009 and 2011. Despite the fact that Turkey has banned synthetic cannabinoids, according to Turkish Statistical Institute (TSI) it was still used by 11- 17 age group in Turkey.

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