TOKSISITAS LOGAM BERATPENDAHULUAN

Orang-orang sudah selalu tepapar dengan logam berat di dalam lingkungan

Cemaran logam pada makanan dan air bisa menyebabkan keracunan

Kandungan logam pada pestisida dan zat-zat terapetik merupakan sumber pemaparan yang membahayakan

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Logam berat menimbulkan efek toksik dengan cara bergabung dengan satu atau lebih gugus reaktif (ligan) yang penting untuk fungsi fisiologis normal

Logam berat, khususnya dalam seri transisi pada sistem periodik, dapat bereaksi di dalam tubuh dengan ligan yang mengandung gugus :oxygen (-OH, -COO -, -OPO3H , >C=O), sulfur (-SH, -S-S-), nitrogen (-NH2 and >NH)

Logam berat yang paling mendapat perhatian akan toksisitasnya adalah

lead (Pb) mercury (Hg)arsenic (As) cadmium (Cd)

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TOKSISITAS LOGAM BERAT

TIMBAL (Pb) Sumber utama pemaparan lingkungan dari logam

adalah tinta, cat bertimbal dan air minum bertimbal.

Kebanyakan toksisitas yang berat dari lingkungan berasal dari pemaparan industri.

Makanan dan minuman asam dapat melarutkan timbal bila dikemas atau disimpan dalam wadah yang tidak tersepuh sempurna, dan dapat menyebabkan keracunan timbal yang fatal bagi manusia.

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Keracunan Timbal

Keracunan akut timbal relatif jarang dan terjadinya karena memakan senyawa timbal larut asam atau menghirup uap timbal

Aksi lokal pada mulut menimbulkan astringensia, rasa haus, dan rasa logam.

Mual, nyeri lambung, dan muntah Tinja berwarna hitam karena PbS,

dan mungkin terjadi diare ataupun konstipasi

Gejala akut pada SSP : paresthesia, and kelemahan otot

Krisis hemolytic akut : anemia berat and hemoglobinuria

Kematian bisa terjadi dalam 1 atau2 hari; jika penderita bertahan dari episode akut, maka tanda keracunan kronik dapat muncul.

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Keracunan Akut

Keracunan Kronis

(Plumbisme)

Gejala plumbisme dibagi ke

dalam 6 kategori :

1. pencernaan

2. neuromuskular

3. SSP

4. hematologik

5. ginjal

6. lain-lain

Efek pd Sal. Cerna Toksisitas lambung kadang mulai

dgn gejala seperti anorexia, kelainan otot, malaise, and

Rasa logam yang persisten muncul secara dini

Bila intoksikasi berlanjut, makaanorexia dan constipation menjadi lebih nyata

Spasme usus, yang menyebabkan nyeri perut yang parah (colic timbal),keadaan yang paling mencekam

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Efek Neuromuskular

• Sindroma neuromuskular (lead

palsy), ditandai dengan

kelemahan otot, terjadi lama

sebelum paralisis dan menjadi

satu-satunya gejala

Efek SSP

• Sindroma SSP (encephalopathy timbal) : manifestasi yang paling serius dari keracunan timbal, jauh lebih banyak terjadi pada anak-2 daripada org dewasa

• Tanda-tanda awal : kaku, vertigo, ataxia, sakit kepala, insomnia, gelisah, dan irritability

Efek Hematologik

• Anemia mikrositik hipokromik, lebih sering teramati pada anak2, secara morfologik serupa dengan akibat defisiensi besi

• Anemia ini diperkirakan karena dua faktor :

1. penurunan daya hidup eritrosit

2. penghambatan sintesis heme.

Efek pd GinjalToksisitas pd ginjal terjadi dlm dua bentuk :

1. Gangguan tubular reversibel (biasanya terlihat setelah pemaparan akut anak-anak pada timbal)

2. Nefropati interstisial ireversibel (lebih umum diamati pada pemaparan timbal industri jangka panjang

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Other Effects Pucat pada wajah

Kelu lidah

Gangguan retina

Penampilan penuaan dini "premature aging," with stooped posture, poor muscle tone, and emaciation;

black, grayish, or blue-black so-called lead line along the gingival margin

Lead also interferes with vitamin D metabolism

decreased sperm count

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Treatment of Lead Poisoning Chelation therapy is indicated in symptomatic

patients or in patients with a blood lead concentration in excess of 50 to 60 mg/dl (about 2.5 mM)

Four chelators :

1. edetate calcium disodium (CaNa2EDTA),

2. dimercaprol (British anti-Lewisite; BAL),

3. D-penicillamine,

4. succimer (2,3-dimercaptosuccinic acid; DMSA; CHEMET)

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MERCURY

Mercury was an important constituent of drugs for centuries as an ingredient in many diuretics, antibacterials, antiseptics, skin ointments, and laxatives

There have been epidemics of mercury poisoning among wildlife and human populations in many countries

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Chemical Forms and Sources of Mercury

three major chemical forms

1. mercury vapor (elemental mercury),

2. salts of mercury,

3. organic mercurials

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Minamata disease caused by methyl mercury (an organic mercury) Minamata is a small town in Japan, a chemical plant

empties its effluent directly into Minamata Bay The plant used inorganic mercury as a catalyst, and

some was methylated before entering the bay

the compound is then taken up rapidly by plankton algae and is concentrated in fish via the food chain

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Chemistry and Mechanism of ActionMercury readily forms covalent bonds with sulfur,

accounts for most of the biological properties of the metal

If sulfur is of sulfhydryl groups, divalent mercury replaces the hydrogen atom to form mercaptides, X-Hg-SR and Hg(SR)2, where X is an electronegative radical and R is protein.

Organic mercurials form mercaptides of the type R-Hg-SR’ capable to inactivate sulfhydryl enzymes so interfering with cellular metabolism and function

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Elemental Mercury Short-term exposure to vapor of elemental mercury may

produce symptoms within several hours :

weakness

chills

metallic taste

nausea

vomiting

diarrhea

dyspnea

cough

feeling of tightness in the chest

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Elemental Mercury Chronic exposure to mercury vapor produces a

more insidious form of toxicity that is dominated by neurological effects

continued exposure to mercury vapor develop psychological changes consist of depression, irritability, excessive shyness, insomnia, reduced self-confidence, emotional instability, forgetfulness, confusion, impatience, and vasomotor disturbances

Common features of intoxication from mercury vapor are severe salivation and gingivitis

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Organic Mercurials Symptoms of exposure to methylmercury are mainly

neurological

visual disturbance

ataxia

paresthesias

neurasthenia

hearing loss

dysarthria

mental deterioration

muscle tremor

movement disorders

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ARSENIC Arsenic is found in soil, water, and air as a common

environmental toxicant

The major source of occupational exposure to arsenic-containing compounds is from the manufacture of arsenical herbicides and pesticides

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Chemical Forms of Arsenic arsenic atom exists in the elemental form and in

trivalent and pentavalent oxidation states

toxicity increases in the sequence of organic arsenicals < As5+ < As3+< arsine (AsH3)

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Mechanism of Action Arsenate (pentavalent) is a well-known uncoupler of

mitochondrial oxidative phosphorylation

The mechanism is related to competitive substitution of arsenate for inorganic phosphate in the formation of adenosine triphosphate, with subsequent formation of an unstable arsenate ester that is rapidly hydrolyzed (arsenolysis)

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Toxicological Effects of Arsenic Cardiovascular System

Gastrointestinal Tract

Kidneys

Skin

Nervous System

Blood

Liver

Carcinogenesis and Teratogenesis

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