1、Toxicity of Metals,All metals are potentially toxic,All metals are potentially toxic at high concentration, even though some of them are also essential.,Metabolism of metals,Inorganic metal compounds无机非金属 A combination of absorption, storage and elimination Organometallic compounds有机金属化合物 Metabolize
2、d by different biochemical pathways,Toxic mechanism,High affinity for essential amino acid side chains e.g. sulfhydryl, histidyl, and carboxyl groups React directly with proteins to alter enzymatic function Bind to cofactors, vitamins and substrates alter biological functions Presence of an excess o
3、f any metal may lead to depletion of essential metals,Chelation Therapy,Chelation is the formation of a metal ion complex with a ligand. The ligand may be monodentate, bidentate, or multidentate (i.e. it may coordinate with using one or two or more donor atoms) Chelating agents are generally non-spe
4、cific mobilize and enhance the excretion of a wide range of metals, including essential metals,Arsenic砒霜，砷,One of the oldest poisons Trivalent arsenic is more toxic than pentavalent arsenic,Arsenic (II),The pyruvate dehydrogenase (PDH) systems, which converts pyruvate to acetyl coenzyme A. DLDH is d
5、ihydrolipoyl dehydrogenase that generates the dihydrolipoamide 1,3-dithiol (arrow) responsible for binding metals. A general toxicity mechanisms for many heavy metals,Two forms in acute arsenic poisoning,Paralytic form large doses are absorbed quickly develop symptoms quickly Constriction of throat
6、followed by dysphagia (difficult to swallow) paralysis death Gastrointestinal form Watery diarrhea caused by paralysis of the central mechanism of the capillary control in the intestinal tract. blood volume and blood pressure shock Disturbed heart action and cause death,Chronic arsenic poisoning,Beg
7、ins as local erythema with burning and itching mottled skin Swelling and vesicular eruptions Melanosis on eyelids, temples, neck and trunk Hyperkaratosis formation of warts Mees line (horizontal white bands across nails) Nasal septum ulceration,Mercury,Liquid metal occurs naturally Obtained by heati
8、ng the widely found sulfide mineral, cinnabar (HgS) Dissolves many other metals to give solid solutions, called amalgams (was used for fillings in dentistry) Mercuric chloride has been used in medicine for more than 3000 years Methylmercury e.g. was once used extensively as an agricultural fungicide
9、,Toxicity of Mercury,Most mercury compounds are very toxic Readily absorbed through skin 1 gram of mercuric chloride lethal dose for an adult human Reaction with the SH groups of respiratory enzymes in a manner similar to arsenic forming S-Hg-S polymers Lipophilic methymercury penetrate nerves bind
10、to cysteines on Acetylcholine receptors neurological dysfunction,Symptoms of Mercury exposure,Exposure to a high concentration of mercury vapor Acute pneumonitis Chronic low level exposure Weight loss, loss of appetite Gingivitis (inflammation of gum) Salivation, irritability, muscular tremors Inges
11、tion of inorganic mercury (II) salts Corrosive effect on the alimentary tract Acute renal failure Prolonged ingestion of mercury (II) salts Irritability, loss of body weight, painful extremities, rash , photophobia,Symptoms of Mercury exposure (II),Methylmercury Damage central nervous system First s
12、ymptom : Paresthesia (burning and pricking sensation) Damage sensory neurons of the cerebral cortex Affect vision, hearing, speech, movement, sensation in hands and feet, intelligence and mental ability Brain size and development are affected in young,Environmental cycling of methylmercury species,S
13、peciation物种 of Mercury,Lead,Melted lead is not poisonous but the compound are toxic The most widely distributed of the toxic elements Enter the environment Smelting of the sulfide ore Use in storage batteries, pipe, solder Use tetraethyl lead to gasoline Lead tetroxide in corrosion-resistant paint L
14、ead monoxide in fine glass Millions of pounds of lead arsenate for insect control in the first four decades of 1900s Contaminates large areas of lands,Plain abdominal radiograph in a 3-year-old patient shows multiple metallic particles due to ingested flakes of lead paint.,Toxicity of lead,Binds to
15、and inactivates SH-containing substrates e.g. DHL (dihydrolipoyl transcetylase) Inhibit heme血红素biosynthesis anemia贫血and cardiovascular symptoms心血管症状 Replace Ca in bone and in biochemical processes Compete with Ca2+ in nerve function neurotoxicity Disturbed Ca metabolism impaired bone and tooth devel
16、opment Lower cytochrome P450 levels affect detoxication解毒 ability Alter brain neurotransmitter神经递质 function,Social社会 mpact of Lead,Subtle effects: hyperactivity多动症, attention span, 9-point reduction in IQ in exposed children (WHO, 1995) Plasma lead level are correlated with antisocial反社会 behavior Ma
17、ny juvenile criminals少年罪犯 show elevated lead in their blood The exposure of inner city kids comes primarily from old lead-based paints. Effects on mammals, birds and aquatic organisms reproduction繁殖, survival, growth,Tin锡,Elemental tin is safe and used as coating on the inside of steel cans Tripheny
18、ltin hydroxide combat fungal grain disease in Europe Tricyclohexyltin hydroxide (cyhexatin) fungicide杀菌剂 on tree fruits However, Tributyltin (TBT) used in antifouling paints防污漆 to keep barnacles船底的附着甲壳动物 away now are known to be extremely toxic to aquatic animals Many states in US have now limited t
19、heir use,Tin can,Tin man,Copper,copper compounds have long been used in medicine and agriculture Verdigris铜绿 (basic copper acetate) as pesticide Bordeaux mixture (cupric hydroxycarbonate) to combat mildew on grapes “bluestone” (cupric sulfate pentahydrate) as an algicide杀藻剂 Copper derivatives are un
20、iformly toxic Using the general toxicity mechanism repel bacteria, fungi, algae, aquatic invertebrates and undesirable fish,Lined copper cooking utensils炊具 can safely be used for most foods.,Speciation of Copper,Copper complexes weakly with Chloride But strongly with humics腐殖质 High toxicity of Cu2+
21、seen in laboratory tests with aquatic animals may not apply equally in the natural environment,Symptoms of Copper intoxication,Chronic exposure to copper in dust, fumes Nasal ulceration and bleeding Various damage to lung Discoloration of the skin Oral ingestion Nausea, vomiting, diarrhea and intest
22、inal cramps Disrupted liver and kidney functions jaundice黄疸 and cirrhosis肝硬变 Hemolytic anemia and death,Nickel镍,Common element Resistant to corrosion腐蚀 industrial and consumer uses US and Canadian 5-cent pieces are 25% Ni and 75% Cu. Nickel compounds are unusually toxic and carcinogenic Inhalation o
23、f Ni 3S2 and NiO and Ni nasal and pulmonary cancer Contact dermatitis Contact the nickel coin rash in sensitive individual May be responsible for a decline in marine life,Symptoms for Nickel intoxication,Hypersensitivity过敏症 Nickel itch redness of hands eczema湿疹 lichenification苔癣样硬化 (scaling) Cancer
24、mortality rates from cancers of the lungs and nasal cavities for Nickel refining workers Exposure to nickel sulfide and nickel oxide malignant tumors恶性肿瘤 in larynx, kidney, prostate前列腺 or stomach Respiratory disorders Exposure to nickel carbonyl interstitial pneumonitis,Cadmium镉 (Cd),Toxic pollutant
25、s used primarily for protective plating, in solder, in Ni-cad batteries Occurs closely associated with zinc Vehicle tires wear down major source of Cd pollution Occurs at relatively high levels in cigarette smoke,Symptoms for Cd intoxication,Acute toxicity Via respiratory route lung edema, fibrosis
26、Dietary intake painful sites spread all over the body, difficulty in walking, bone fractures Chronic and low exposure Cd bound to metallothionein金属硫蛋白 released from the liver move to kidney via blood Cd-metallothionein accumulates in tubular cells affect proximal tubules reabsorption and proteinuria蛋白尿 kidney stones and softening of the bone due to mineral loss,
