腐蚀性毒物和金属毒物中毒 /Corrosives

poison and Metallic Poisons

Luyang Tao

Corrosive poison

Accidental Divide into five groups:

1)acids

2)alkalis

3)mentallic salts

4)halogens

5)gases

General feature of corrosive poisoning

Ingestion Severe abdominal pain and marked thirstVomited matter Death from shock and collapse Enters air – suffocation A few days death – gastric perforation

and peritonitisStarvation

Poisoning from mineral acids

Sulphuric acid

Nitric acid

Hydrochloric acid

Acids

Hydrochloric As with most acids, not usually used to kill someone, but can be used to dispose of the corpse afterwards. Corrosive and colorless.

Nitric Usually colorless, though goes brown when oxidized.

SulphuricColorless. A dehydrating agent that extracts water from the body. Is strong enough to eat through bones as well as flesh. This process takes about 4 hours.

Alkalis

Potassium hydroxide (Caustic potash) Very corrosive. If consumed, it burns then mouth and stomach, then makes the lips and tongue swell. Vomiting is of a brown substance, with bits of dead skin and flesh in it. Skin is cold and clammy and the heart beat feeble and rapid. Death comes from damage to the stomach, asphyxia to the corrosion of the larynx, or congestion of the lungs due to breathing dead material. Also sometimes used to dispose of bodies.

Sodium hydroxide Similar to above. Often found in household cleaners

Ammonia Colorless and smelly. Not usually used as a murder weapon. If it is consumed in its liquid form, death is usually from corrosion of the larynx. Lungs are congested and frothy, and the blood is dark and resistent to clotting. Exposure to ammonia gas gives a sensation of suffocation, a burning sensation in the mouth and stomach, and vomiting which contains blood and smells of

Lye (NaOH)

The severity of injuries depends in part on the form of the lye ingested. Originally, it was available only in a crystalline form. Accidental ingestion was difficult, because only a few crystals caused severe pain, prompting a rapid cessation of such intake. Individuals attempting suicide commonly diluted the crystals with water to produce a solution of relatively low alkaline

Mental poisoning

Mental poisoning

Pure mental (exception mercury and lead ) rarely toxic.

Mental salts posses poisonous properties of varying intensity.

Radioactive metallic compounds damage the tissues (bone and bone marrow)

Inorganic compounds effects, organic compounds effects delay.

Cadmium

Cadmium (Cd) Relatively new metal in terms of humans Sources:

natural rock weathering copper, lead and zinc smelting auto

exhaust cigarette smoke (a cigarette contains

1-2 ug Cd) Uses:

metal plating nickel-cadmium batteries solders paint pigments (blue) plastic stabilizers photographic chemicals fungicides

readily absorbed and accumulated in plants

Food as most common route of exposure for general population

Cadmium (Cd)pharmacokinetics: inhalation:

smelters, cigarette smoke 15-50% absorbed

ingestion: main source is liver and kidney of meats 6% absorbed, greater if deficient in

calcium, zinc or iron Shenyang Copper Smelter

Cadmium (Cd)pharmacokinetics: distribution:

bound to albumin in plasma and red blood cells

transported to liver, pancreas, prostate and kidney, with eventual transfer to kidney

50-75% of total body Cd is found in liver and kidney

Metallothionein: protein rich in cysteine traps Cd esp. in kidney

synthesis induced by Cd Elimination: urine

half-life in humans is 20 - 30 years

Metallothionein

Cadmium (Cd)Toxicity mechanisms:

binding to –SH groups competing with Zn and Se for inclusion

into metalloenzymes competing with calcium for binding sites

(calmodulin) Kidney toxicity:

free Cd binds to kidney glomerulus proximal tubule dysfunction

Cadmium (Cd)Toxicity Lung toxicity:

edema and emphysema by killing lung macrophages

Skeletal effects: Osteoporosis and osteomalacia

(pseudofractures) Cancer:

carcinogenic in animal studies ~8% of lung cancers may be

attributable to Cd

Cadmium detection and treatment What would cause you to suspect Cd

toxicity? What tests could you do to detect exposure

or effects? detected via increased excretion of

proteins, amino acids and calcium

What could you prescribe for treatment? Acute inhalation: fluid replacement,

mechanical ventilation Acute ingestion: emesis and gastric

lavage Chronic:

chelation therapy is ineffective so only treatment is to remove source

Cadmium (Cd)Epidemics/case studies

Japan (1940s) effluent (outflow) from a lead-

processing plant washed over adjacent rice paddies for many years

rice accumulated high level of Cd

community was poor (and therefore malnourished with respect to calcium)

acute toxicity: renal failure,anemia, severe muscle pain

named "Itai-Itai" disease ("ouch, ouch") Itai-itai victim

Cadmium (Cd)Epidemics/case studies

Sewage waste disposal

contains high levels of N and P, and organic matter, so makes sense to use as fertilizer on fields

also can contain Cd, which is readily accumulated in plants

livestock grazing on fields can accumulate Cd in liver and kidney 6-8x as much as sheep

grazing on clean fieldsLand application

Arsenic

Arsenic (As) Chemistry:

extremely complex because it can exist in metallic form, can be in trivalent and pentavalent state (charge of 3+ or 5+), and can be organic or inorganic

widely distributed in nature (variety of forms)

Sources: smelting of gold, silver, copper, lead and zinc ores combustion of fossil fuels agricultural uses as herbicides and fungicides cigarette smoke occupational: largest source is manufacture of pesticides and

herbicides

Environmental fate: found in surface and groundwater through runoff accumulates in plants if soil conditions are right bioaccumulates in aquatic ecosystems (so fish consumption is a

source)

From: Klaassen et al., Chap. 19, Philp, Chap. 6

Sources of As Eating food, drinking water, or breathing air containing arsenic.

Herbal medicines (India/Pakistan Ayurvedic” remedies Breathing contaminated workplace air. Breathing sawdust or burning smoke from wood treated with arsenic. Living near uncontrolled hazardous waste sites containing arsenic. Living in areas with unusually high natural levels of arsenic in rock.

Arsenic: the poison of choice

Napoleon and Paris Green

Arsenic (As) pharmacokinetics and dynamics:

absorbed via inhalation, ingestion and dermal exposure

mimics phosphate in terms of uptake by cells Detoxified by methylation: decreased rates lead to

increased toxicity (individual susceptibility) Can cross placenta accumulates in liver, kidney, heart and lung - later

in bones, teeth, hair, etc. half-life is 10 hr, excretion via kidneys

Arsenic Toxicity Mechanisms

binds to sulfhydryl groups (and disulfide groups), disrupts sulfhydryl-containing enzymes (As (III)) inhibits pyruvate and succinate oxidation

pathways and the tricarboxylic acid cycle, causing impaired gluconeogenesis, and reduced oxidative phosphorylation

targets ubiquitous enzyme reactions, so affects nearly all organ systems

substitution for phosphorus in biochemical reactions Replacing the stable phosphorus anion

in phosphate with the less stable As(V) anion leads to rapid hydrolysis of high-energy bonds in compounds such as ATP. That leads to loss of high-energy phosphate bonds and effectively "uncouples" oxidative phosphorylation.

Arsenic Toxicity organic arsenicals>inorganic

arsenicals>metallic forms trivalent>pentavalent acute: severe abdominal pain, fever,

cardiac arrhythmia chronic: muscle weakness and pain,

gross edema, gastrointestinal disturbances, liver and kidney damage, swelling of peripheral nerves (neuritis), paralysis liver injury: jaundice peripheral vascular disease -

blackfoot disease chronic drinking water exposure

in Taiwan and Chile cancer (skin, lung. Maybe other

organs)

Arsenic Toxicity skin disease:

keratosis of palms and soles, and hyperpigmentation

Medical uses: Chemotherapy Causes cancer but also cures it?

Perhaps 2 mechanisms? Arsenic trioxide approved for acute

promyelocytic leukemia (APL) Used to be used 100 years ago as

chemo agent, dropped when others were invented

New interest based on Chinese therapies 70% remission rate Causes cancer cells to puff up and die Mechanism: supression of hTERT

gene, which codes for building blocks of telomerase, which keeps the end parts of chromosomes intact

Result: chromosomes fuse end-to end

Case study

Arsenic detection and treatment

What would cause you to suspect As toxicity?

What tests could you do to detect exposure or effects? Mee's lines: white lines on

fingernails can be used to determine chronology of exposure

What could you prescribe for treatment? Gastric lavage, activated charcoal Hemodialysis BAL chelation

WWII

Arsenic Problems: Bangladesh As leached from underground sources into village wells of 1 million people

62% of wells tested exceeded WHO standard ~ 35 million people exposed above US EPA standard

200,000 people suffering from As-induced skin lesions problem may have been exacerbated by large scale withdraw of groundwater for

irrigation or by extensive use of fertilizers

From: Klaassen et al., Chap. 19, Philp, Chap. 6

Arsenic On the Playground

Pressure treated wood CCA: 22 percent pure arsenic A 12-foot section of pressure-

treated lumber contains about an ounce of arsenic, or enough to kill 250 people.

"In less than two weeks, an average five-year-old playing on an arsenic-treated playset would exceed the lifetime cancer risk considered acceptable under federal pesticide law."

EPA, 2004, banned from residential use

Poisoned Playgrounds: EWG

Barium

Barium Used in various soluble compounds. Barium carbonate is used as rat bait. (Insoluble compounds, eg barium sulphate, are harmless and used in barium meal given before X-raying digestive system.) Is an irritant poison, which causes vomiting and thus can get rid of the fatal dose. Symptoms Vomiting. Increased pulse and raised blood pressure. Also attacks central nervous system. Death by heart failure or paralysis. Post-mortem appearance Inflamed throat, stomach, rectum etc.

Lead

Lead Usually used as one of its salts eg lead acetate. Symptoms are severe stomach pains, vomiting, coms then death. Repeated small doses can cause mental deterioration.

Child Health

Effects of Amount on Response

Effects of Size on Response

• Dose Response Issues

• Higher metabolic rate

• Different nutritional requirements

• Rapidly dividing & migrating cells

• Immature organs• Different Behaviors (hand to mouth)

Susceptibility of Children

Lead In Homes

A house painter affected by chronic lead poisoning. Wasted muscles and wrist drop are tell-tale symptoms of lead poisoning.

Lead Health Effects

Children more vulnerable than adults• Orally consumed lead absorbed in place of calcium

• CHILDREN absorb 30-50% of oral lead

• ADULTS absorb 5-10% of oral lead

• Increased absorption during pregnancy

Childhood effects• Decreased intelligence (lower grades)

• Hyperactivity (higher school dropout rate)

• Growth retardation

• Effects at blood lead levels of 10 µq/dl

The symptoms of chronic lead poisoning are abdominal cramps, vomiting, constipation, lethargy, anemia, weight loss, muscle paralysis, nephropathy, and convulsions. Death is uncommon. When it does occur, it most often involves children in tenement areas who have a history of pica.

Children under 6 years old and pregnant women are the most vulnerable to lead and are considered to have "elevated" lead levels if their blood test results are greater than 10 ug/dL. Although there has been a dramatic decline in national blood lead levels over the past 10-15 years, childhood lead poisoning continues to be a major, preventable environmental health problem.

In recent decades the dominant source of lead exposure to humans has been from emissions of motor vehicles operating on leaded petrol. 

Antimony

In the elemental form-- nontoxic ,heated the metal vapourises forming antimony trioxide

Antimony

Inorganic compounds Organic compounds Action Treatment

Stibine

Mercury

mercury in dental amalgam fillings--sadly trumps all other uses both in magnitude of mass product and unrelenting harm to the human body.

Mercury

Absorption:

skin, stomach, lungs, mucosa of the vagina, bladder and rectum

distribution: liver kidneys, intestines and salivary glands

elimination: renal

Mercury

Pharmacological action

like arsenic

Inorganic mercury compounds

acute Mercury

Signs and symptoms of poisoning acute: oral ingestion- mercuric chloride

–mucosa of the gastrointestinal corroded

Treatment life-saving gastric lavage BAL penicillamine CaEDTA

gastrointestinal corroded

Mercury

Post mortem appearance

CORROSION

Fatal dose 1-4g

Chronic Mercury

Chronic Mercury

Signs and symptoms of poisoning

skin – pale

mercurial tremor

mental affection - erethism

Diagnosis

mercurial tremor

Breathing mercury's fumes over a long period of time causes erethism, a disorder characterized by nervousness, irritability and personality changes.

Chronic Mercury

Treatment

organic mercury compounds