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TOKSİKOLOJİ’DE GÜNCELLİK
KALICI KİMYASAL KİRLİLİKLERİN KRONİK
HASTALIKLARA YOL AÇMA RİSKLERİ
Prof Dr Seyfullah Oktay ARSLAN
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İÇERİK
Tanımlar
Sorunlar
İmkanlar
Çözüm Önerileri!!!
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TANIMLAR
TOKSİKOLOJİ, TOKSİKOLOJİ UZMANI
Canlıların yaşadığı ortamlardan, ağız, deri ve
solunum yoluyla isteyerek ya da istemeyerek,
kaza ya da kasten aldığı/maruz kaldığı kimyasal
yapıdaki unsurların, canlı yapılarla olan zarar
verici etkileşimlerini inceler.
Dışardan alınan besin yapıları dışındaki tüm
kimyasal yapılar genel anlamda ksenobiotik diye
adlandırılır.
Canlıların ksenobiotiklere karşı güvenlik
sınırları belirlenmektedir.
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TANIMLAR
TOKSİKOLOJİNİN DALLARI
Klinik Toksikoloji
Mesleki Toksikoloji
Çevre Toksikolojisi
Ekosistem Toksikolojisi
Adli Toksikoloji
Analitik Toksikoloji
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TANIMLAR
ZEHİRLENMELER
Akut
Tek seferde ya da 1-2 gün
içinde birkaç defada maruz
kalındığında toksik etkiler
oluşması
Kronik
Daha uzun süre maruz
kalmalar
Su, gıdalar, atmosfer
Kasıtlı
Kazaen
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TANIMLAR
ZEHİRLENMELER
Bilinen bir toksik maddenin etkisiyle oluşacak zehirlenmenin derecesi maruz kalma yolu ve süresine bağlı olarak şekillenir.
Acceptable daily intake (ADI)
The Food and Agriculture Organization and the World Health Organization (FAO/WHO)
Threshold limit values (TLVs) (mg/m3):
The American Conference of Governmental Industrial Hygienists
Günde 8 saat veya haftada 40 saat çalışma süresi için defalarca maruz kalındığında o kimyasal maddenin istenmeyen etki göstermeyen konsantrasyonudur.
Kanser Slop faktörü (mg/kg/gün)(oral,dermal)
Karsinojenik riski olanlar için bir ömür boyu (70 yıl) alınabilecek dozu tanımlar.
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SORUNLAR
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I. AIR POLLUTANTS
Five major substances account for about 98% of air pollution:
carbon monoxide (about 52%),
sulfur oxides (about 14%),
hydrocarbons (about 14%),
nitrogen oxides (about 14%),
and particulate matter (about 4%).
Ambient air pollution has been implicated as a contributing factor in bronchitis, obstructive ventilatorydisease, pulmonary emphysema, bronchial asthma, and
lung cancer
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CARBON MONOXİDE
The average concentration of CO in the atmosphere is
about 0.1 ppm.
Carboxyhemoglobin
The brain and the heart are the organs most affected
The administration of oxygen
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CARBON MONOXİDE
The principal signs of CO intoxication are those of hypoxia
and progress in the following sequence:
(1) psychomotor impairment;
(2) headache and tightness in the temporal area;
(3) confusion and loss of visual acuity;
(4) tachycardia, tachypnea, syncope, and coma; and
(5) deep coma, convulsions, shock, and respiratory failure
Carboxyhemoglobin levels below 15% rarely produce
symptoms; collapse and syncope may appear around 40%;
above 60%, death may ensue. Prolonged hypoxia and
posthypoxic unconsciousness can result in irreversible
damage to the brain and the myocardium
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TLV (ppm)
Compound TWA1 STEL2
Benzene 0.5 2.5
Carbon monoxide 25 NA
Carbon tetrachloride 5 10
Chloroform 10 NA
Nitrogen dioxide 3 5
Ozone 0.05 NA
Sulfur dioxide 2 5
Tetrachloroethylene 25 100
Toluene 50 NA
1,1,1-Trichloroethane 350 450
Trichloroethylene 50 100
1TLV-TWA is the concentration for a normal 8-hour workday or 40-hour
workweek to which workers may be repeatedly exposed without adverse effects.
2TLV-STEL is the maximum concentration that should not be exceeded at any
time during a 15-minute exposure period.
Threshold limit values (TLV) of some common air
pollutants and solvents. (NA = none assigned)
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I. AIR POLLUTANTS
Sorun: Akut ve kronik, kasıtlı ve kazaen zehirlenme
Hava kirliliği
Çözüm: Temiz hava
Tedbir: Her kapalı ortamın havasının değiştirilmesi, cam açılması
(yabancı ortamlarda mümkünse istirahat halinde de)
Yabancı ortamlarda kapalı ortamın havasının taşınabilir cihazla ölçümü
Hiperbarik oksijen uygulaması-tedavide- her zaman iyi olmayabilir.
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II.SOLVENTLER
Halogenated Aliphatic Hydrocarbons
Aromatic Hydrocarbons
Daha çok mesleki maruziyetlerde ve bağımlılıkta
akut ve kronik şekillerde görülür
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HALOGENATED ALİPHATİC HYDROCARBONS
carbon tetrachloride,
chloroform,
trichloroethylene,
tetrachloroethylene (perchloroethylene), and
1,1,1-trichloroethane
Central nervous system depression, liver injury, kidney injury, and some degree of cardiotoxicity.
Chronic exposure to tetrachloroethylene can cause impaired memory and peripheral neuropathy
Hepatotoxicity is also a common toxic effect
There is no specific treatment for acute intoxication resulting from exposure to halogenated hydrocarbons. Management depends on the organ system involved.
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AROMATİC HYDROCARBONS
Benzene is widely used for its solvent properties and as an intermediate in the synthesis of other chemicals.
The acute toxic effect of benzene is depression of the central nervous system.
Exposure to 7500 ppm for 30 minutes can be fatal. Exposure to concentrations larger than 3000 ppm may cause euphoria, nausea, locomotor problems, and coma; vertigo, drowsiness, headache, and nausea may occur at concentrations ranging from 250 to 500 ppm.
No specific treatment exists for the acute toxic effect of benzene.
Chronic exposure to benzene can result in injury to the bone marrow; aplastic anemia, leukopenia, pancytopenia, or thrombocytopenia may occur.
The early symptoms of chronic benzene intoxication may be rather vague (headache, fatigue, and loss of appetite).
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AROMATİC HYDROCARBONS
Toluene (methylbenzene), a central nervous system
depressant.
Exposure to 800 ppm can lead to severe fatigue and ataxia;
10,000 ppm can produce rapid loss of consciousness. Chronic
effects of long-term toluene exposure are unclear because
human studies indicating behavioral effects usually concern
exposures to several solvents, not toluene alone. In limited
occupational studies, however, metabolic interactions and
modification of toluene's effects have not been observed in
workers also exposed to other solvents
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III.INSECTICIDES
Organochlorine insecticides
Organophosphorus Insecticides
Carbamate Insecticides
Botanical Insecticides
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Chemical
ClassCompounds
Toxicity
Rating1 ADI2
DDT and
analogs
Dichlorodiphenyltrichloroethan
e (DDT)4 0.005
Methoxychlor 3 0.1
Tetrachlorodiphenylethane
(TDE)3
Benzene
hexachlorides
Benzene hexachloride (BHC;
hexachlorocyclohexane)4 0.008
Lindane 4 0.008
Cyclodienes Aldrin 5 0.0001
Chlordane 4 0.0005
Dieldrin 5 0.0001
Heptachlor 4 0.0001
Toxaphenes Toxaphene (camphechlor) 4
1Toxicity rating: Probable human oral lethal dosage for class 3 = 500-5000 mg/kg, class 4 =
50-500 mg/kg, and class 5 = 5-50 mg/kg. (See Gosselin et al, 1984.)
2ADI = acceptable daily intake (mg/kg/d).
Organochlorine insecticides
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ORGANOPHOSPHORUS INSECTİCİDES
CompoundToxicity
Rating1 ADI2
Azinphos-methyl 5 0.005
Chlorfenvinphos 0.002
Diazinon 4 0.002
Dichlorvos 0.004
Dimethoate 4 0.01
Fenitrothion 0.005
Leptophos
Malathion 4 0.02
Parathion 6 0.005
Parathion-methyl 5 0.02
Trichlorfon 4 0.01
1Toxicity rating: Probable human oral lethal dosage for class 4 = 50-500
mg/kg, class 5 = 5-50 mg/kg, and class 6 = 5 mg/kg. (See Gosselin et al,
1984.)
2ADI = acceptable daily intake (mg/kg/d).
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CARBAMATE INSECTİCİDES
CompoundToxicity
Rating1 ADI2
Aldicarb 6 0.005
Aminocarb 5
Carbaryl 4 0.01
Carbofuran 5 0.01
Dimetan 4
Dimetilan 4
Isolan 5
Methomyl 5
Propoxur 4 0.02
Pyramat 4
Pyrolan 5
Zectran 5
1Toxicity rating: Probable human oral lethal dosage for class 4 = 50-500 mg/kg, class 5 =
5-50 mg/kg, and class 6 = 5 mg/kg. (See Gosselin et al, 1984.)
2ADI = acceptable daily intake (mg/kg/d).
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BOTANİCAL INSECTİCİDES
Insecticides derived from natural sources include nicotine,
rotenone, and pyrethrum. Nicotine is obtained from the
dried leaves of Nicotiana tabacum and N rustica.
Rotenone is obtained from Derris elliptica, D mallaccensis,
Lonchocarpus utilis, and L urucu. The oral ingestion of
rotenone produces gastrointestinal irritation.
Conjunctivitis, dermatitis, pharyngitis, and rhinitis can
also occur. Treatment is symptomatic.
Pyrethrum consists of six known insecticidal esters:
pyrethrin I, pyrethrin II, cinerin I, cinerin II, jasmolin I,
and jasmolin II. Pyrethrum insecticides are not highly toxic
to mammals
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III.INSECTICIDES
Başlıca Ziraat’ta mesleki, kasıtlı, akut ve kronik
şekillerde tüm maruziyetlerle görülebilir.
İnsan ve diğer canlıların çok geniş bir yüzleşme
alanına sahip olduğu konudur
Gıda zincirinde bulunması önemli bir maruziyet
nedenidir.
1980 ler öncesi Organik klorlu bileşiklerin
kullanım durumu???
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IV. HERBICIDES
Chlorophenoxy Herbicides
2,4-Dichlorophenoxyacetic acid (2,4-D),
2,4,5-trichlorophenoxyacetic acid (2,4,5-T),
Bipyridyl Herbicides
Paraquat
Glifosat?
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CHLOROPHENOXY HERBİCİDES
2,4-Dichlorophenoxyacetic acid (2,4-D), 2,4,5-
trichlorophenoxyacetic acid (2,4,5-T), and their salts and esters
In humans, 2,4-D in large doses can cause coma and generalized muscle
hypotonia.
The toxicologic profile for these agents, particularly that of 2,4,5-T, has
been confusing because of the presence of chemical contaminants
(dioxins) produced during the manufacturing process (see below).
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most important of
these contaminants
Paraquat is the most important agent of this class.
Paraquat accumulates slowly in the lung by an active process and
causes lung edema, alveolitis, and progressive fibrosis.
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V. ENVIRONMENTAL POLLUTANTS
Polychlorinated biphenyls (PCBs)
Polychlorinated dibenzo-p-dioxins (PCDDs)
Endocrine Disruptors
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POLYCHLORİNATED BİPHENYLS
These chemicals are highly stable and highly
lipophilic, poorly metabolized, and very resistant to
environmental degradation; they bioaccumulate in
food chains.
Food is the major source of PCB residues in
humans.
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POLYCHLORİNATED BİPHENYLS
A serious exposure to PCBs occurred in Japan in 1968 as
a result of cooking oil contamination with PCB-
containing transfer medium (Yusho disease).
Possible effects on the fetus and on the development of
the offspring of poisoned women were reported. It is now
known that the contaminated cooking oil
Workers occupationally exposed to PCBs have exhibited
the following clinical signs: dermatologic problems
(chloracne, folliculitis, erythema, dryness, rash,
hyperkeratosis, hyperpigmentation), some hepatic
involvement, and elevated plasma triglycerides.
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DIOXINS
The polychlorinated dibenzo-p-dioxins (PCDDs), or dioxins, have been mentioned above as a group of congeners of which the most important is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
Polychlorinated dibenzofurans (PCDFs) and coplanar biphenyls.
While PCBs were used commercially, PCDDs and PCDFs are unwanted by-products that appear in the environment as contaminants because of improperly controlled combustion processes.
Like PCBs, these chemicals are very stable and highly lipophilic. They are poorly metabolized and very resistant to environmental degradation.
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TCDD
immunotoxicity,
teratogenicity, and
carcinogenicity.
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ENDOCRİNE DİSRUPTORS
Phytoestrogens, mycoestrogens, DDT, PCBs, PCDD
The potential hazardous effects of some chemicals in
the environment are because of their estrogen-like or
antiandrogenic properties.
Compounds that affect thyroid function are also of
concern.
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METALLERİN TOKSİK
ETKİLERİ
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Metalleri diğer toksik maddelerden ayıran en önemli özellikleri, insanlar tarafından ne
oluşturulabilir nede yok edilebilir olmalarıdır.
Periyodik tablodaki 105 elementin yaklaşık 80’ini
metaller oluşturur.
Birçok metal, insan ve hayvanlar için esansiyeldir. Esansiyel olanlar, eksikliklerinde olduğu gibi fazla miktarlarda alındıklarında da vücut homeostazını bozarak toksik etki oluşturabilirler.
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Bugün “endüstriyel metaller” olarak
nitelendirilen yaklaşık 50 metal ve alaşımı çeşitli
amaçlarla kullanılmaktadır.
Ayrıca metaller ve tuzları hekimlikte ilaç,
pestisit (fungusit, insektisit, herbisit, rodendisit
gibi) olarak da kullanılmaktadır.
30 civarında metalin insanlarda toksisite
oluşturduğu bilinmektedir.
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Metaller, insanlar tarafından veya hava, su, toprak ve besinlere çevresel taşınım sonucu besinler ve içme suları ile organizmaya girebilirler.
Besinlerin normal bileşeni olabildikleri gibi kirlilik olarak da bulunabilirler.
İnsan vücudu için esansiyel olan ve olmayan metaller başta besinler olmak üzere diğer bazı yollarla (su, hava gibi) alınmaktadır.
Böylece “vücut metal yükü “ oluşmakta; bazıları ise (alüminyum, kurşun ve kadmiyum gibi) yaş ile birikerek vücuttaki konsantrasyonları artmaktadır.
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METALERE MARUZİYET
Kütahya Emetteki yer altı sularının arsenikle kirlenmesi
Japonya’da Minamata bölgesinde cıva ile kontamine olmuş
balıkların yenmesi ile görülen zehirlenme olayı
Selenyumca zengin topraklarda yetişen bitkilerde selenyum
birikim gösterir. Hayvan ve insanlara geçerek keratindeki
kükürdün yerini alarak birikir
Metalden yapılmış veya metal bileşikleri içeren besin
kaplarından metaller besinlere geçebilir
Endüstride metal zehirlenmeleri başlıca inhalasyon yolu ile
olmaktadır. Ancak talyum, alkil kurşun, nikel, arsenik ve
berilyum gibi metallerin deri yolu ile de absopsiyonları önemlidir
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METAL TOKSİSİTELERİ
Esansiyel elementlerle etkileşim
kurşun kalsiyuma benzer metabolizması ile kemik mineralizasyonunu, demir ve çinkonun yerini alaraktahem metabolizmasını etkiler
Metal-protein komplekslerinin oluşumu
Metallotioneinler (sülfidril grubu içeren proteinler) kadmiyum, çinko, bakır ve diğer metallerle kompleks oluştururken, ferritin ve hemosiderin intrasellüler demir-protein kompleksleridir
İmmün sistem
platinle oluşabilen deri ve bronşiyal hipersensitivitereaksiyonları, organik altın bileşikleri ile oluşabilen trombositopeni, nikel ve kroma maruziyetle gelişebilen kontakt dermatit, berilyum ve zirkoniyumla oluşabilen granülomalar gibi
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Kaynak: Casarett & Doull’s Toxicology “The Basic Science of Poisones”, Curtis Klaassen Publisher: Mc Graw Hill 2001, 6th Edition
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International Agency for Research on
Cancer (IARC), kimyasal maddeleri insandaki
karsinojenik etki risklerine göre beş gruba
ayırmıştır:
Grup 1. İnsanda Karsinojenik Etkililer
Arsenik ve bileşikleri, kadmiyum, krom (6
değerli), nikel ve bileşikleri bu gruptadır.
Grup 2A. İnsanda Karsinojenik Etki
Olasılığı Bulunanlar
Cisplatin bu grupta yer almaktadır.
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Grup 2B. İnsanda Muhtemelen
Karsinojenik Etkili Olanlar
Kurşun ve anorganik bileşikleri bu gruptadır.
Grup 3. İnsandaki Karsinojenik Etkileri
Yönünden Sınıflandırılabilir Olmayanlar
Grup 4. İnsanda Karsinojenik Etkisi
Olmayanlar
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Ağır Metallerin TLV Değerleri
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Kaynak: Ellenhorn’s Medical Toxicology Matthew J. Ellenhorn, 1997
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KASITLI ZEHİRLENMELER
Arsenik ve diğer
metaller
Zehirli bitkiler
Baldıran
Kürar
CO
Siyanür
Arsenik
Organik fosforlular
Savaş gazları,somon
Radyoaktif ürünler
Polonyum
Virüs, şarbon, kuduz vs
K+
CO
Warfarin
Dioksin
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Alexander Litvinenko ve Arafat Vakıası
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Alexander Litvinenko ve Arafat Vakıası
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SEMİN DİAGN PATHOL. 2009 FEB;26(1):61-7.
DEATH BY POLONİUM-210: LESSONS LEARNED FROM THE MURDER OF FORMER
SOVİET SPY ALEXANDER LİTVİNENKO.
The medical response to radiation--whether the result of radiological warfare, terrorist deployment of improvised radiation dispersal weapons, political assassination, occupational or industrial accidents or the medically radiated patient remains one of the least taught among all disciplines within medical education. In the aftermath of 9/11 among medical vulnerabilities to toxicant threats, of all the categories of weapons of mass destruction (WMD)--whether using the CBRNE (chemical, biological, radiological, nuclear, explosive) or NBC (nuclear, biological, chemical) acronym--radiation is the least taught in professional schools, responder cultures or civil preparedness organizations. To date, few health care professionals (HCP) possess the fundamental knowledge or skills to identify and diagnose, let alone treat a radiation victim; this vulnerability made even more obvious in the aftermath of the high profile assassination of former Russian agent Alexander Litvinenko. He was poisoned with Polonium210. Radioactive substances are ubiquitous with radiation sources being in or transported through virtually every region nationwide. It is essential to incre ase preparedness among community and rural health care facilities as well as urban and university hospitals. Managing radiation injuries effectively requires access to specialized equipment and expertise. Radiation sickness is progressive and may require acute, critical and long-term care throughout the course of illness. Regardless of the source, preparedness rests upon acknowledging a threat exists and dedicating the resources to address the risks including the enhancement of training and equipment. Mass or individual exposures to radiation present unique challenges to the entire response continuum from law enforcement, first responders and emergency medical care. Increased education about and practice in responding to radiological threats is essential to enhance preparedness.
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Victor Yushchenko Vakıası
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Somali Korsanları Vakıası
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Karadeniz Vakıası???
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Marmara Vakıası???
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Tarım
Sanayi
Şehir
Dilovası Vakıası???
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Şehir Tarım
Sanayi
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HELAL VE TEMİZ BESLENME
" Ey îmân edenler! Sizi rızıklandırdığımız şeylerin temiz
olanlarından yiyin ve eğer sâdece O’na kulluk ediyorsanız,
Allah’a şükredin.” (2/Bakara 172)
“Ey İnananlar! Allah'ın size helal ettiği temiz şeyleri
haram kılmayın, hududu da aşmayın, doğrusu Allah
aşırı gidenleri sevmez.”(5/maide 87)
“Dilleriniz yalana alışageldiğinden dolayı, Allah’a karşı yalan
uydurmak için, “Şu helâldir”, “Şu haramdır” demeyin.
Şüphesiz, Allah’a karşı yalan uyduranlar, kurtuluşa
eremezler.” (16/Nahl 116)
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BESLENME
THSK besin güvenliğinden bahsederken sadece
mikrobik kontrolü değerlendirme altına
almaktadır
Kimyasal kirlilik güvenliği???
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TEŞEKKÜRLER