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Toxicology > Metal Toxicity > Flashcards

Metal Toxicity Flashcards

1
Q

Major toxic metals

A
  • Arsenic (As)
  • Mercury (Hg)
  • Lead (Pb)
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2
Q

Essential metals

A
  • Copper (Cu)

- Zinc (Zn)

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3
Q

Heavy metals based on..

A

atomic weight

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4
Q

Metals

A
  • naturally occurring elements

- introduced to humans and the environment through industrial, agricultural, and medical activities

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5
Q

Difference compared to other toxicants

A
  • do not quickly break down in the body or environment

- essential for cell function

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6
Q

exerted toxic effects

A
  • inhibit enzyme function
  • oxidative damage (lose or gain 1 electron)
  • replace other metals by binding to molecular targets
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7
Q

Metal types

A
  • major toxic metals
  • essential metals
  • medicinal metals
  • minor toxic metals from technology
  • toxic metalloids
  • non-metallic elemental toxicants
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8
Q

Medicinal metals

A
  • Bismuth subsalicylate
  • increase water absorption
  • kill diarrhea causing bacteria
  • antacid
  • cause black stool and tongue
  • interact with various drugs
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9
Q

Critical factors for relative toxicity (in general)

A

-route of exposure, dose, duration and frequency of exposure

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10
Q

Import factors for metal toxicity

A
  • Age (younger and older are more sensitive)
  • Sex
  • Genetics (adaptive genotypes)
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11
Q

Types of proteins that influence the disposition in the body

A
  • non-specific binding to proteins move metals throughout the body (albumin and hemoglobin)
  • metalolthioneins
  • transferrin
  • ferritin
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12
Q

metallothioneins

A
  • specific metal binding proteins
  • high affinity for Zn, Cd, Cu, Hg
  • protect cell from oxidative damage
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13
Q

Transferrin

A

-binds to Fe in the plasma to help transport it across cell membranes

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14
Q

Ferritin

A
  • primary cellular storage site for Fe
  • sequester Fe in the cell if necessary
  • binds Cd, Zn, beryllium, Al
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15
Q

Pharmacology uses

A
  • platinum, gallium, titanium compounds for cancer chemotherapy
  • Al in antacids
  • Bismuth
  • Au for rheumatoid arthritis
  • Lithium for bipolar disorder
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16
Q

Pb (lead)

A
  • found in ores
  • mined
  • byproduct of smelting other metals
  • dense and malleable
  • heaviest non-radioactive metal
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17
Q

Past uses of Pb

A
  • Turkey
  • Romans=make plumbing and dishwear, wine sweetner
  • Egypt=Kohl for mascara
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18
Q

Pb limit in cosmetics

A

-health canada limit is 10 micrograms/gram

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19
Q

Pb in gasoline

A
  • 1936=90% of gas sold had TEL in it
  • 1972=phased out of gas
  • 1979=showed low doses of lead caused developmental defects
  • 1982=fully banned
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20
Q

Thomas Midgley

A
  • General Motors

- tetraethyl lead (TEL) could replace ethanol in gas

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21
Q

Effects of Pb exposure

A
  • utero and children lower IQ due to neurotoxicity

- drop in Pb levels drop in crime rates

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22
Q

Sources of Pb still encountered

A
  • Old paint
  • Old piping
  • Batteries
  • Glass and ceramics
  • Solder (electronics)
  • Soil and food (principle exposure source)
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23
Q

Old paint

A
  • added to oil paints until 1970s=10-15%
  • Canada Hazardous Products Act reduced to max 0.5%
  • 2010 reduced to 0.009%
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24
Q

Old piping

A
  • pipes and solder joints for brass piping

- Winnipeg uses orthophosphate in its water supply to decrease Pb levels

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25
Q

Batteries

A

88% of all lead now used is in batteries

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26
Q

Pb Ammunition

A
  • banned in lots of place

- can lead to toxic effects and accumulate in wildlife

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27
Q

Flint water crisis

A
  • started using lead piping
  • High levels in water supply
  • high levels of trihalomethanes detected so ferric chloride added to improve removal of organic matter
  • increase chloride already in the water, water was now corrosive
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28
Q

Corrosion control of lead

A

-use orthophosphates to reduce the amount of lead leaching in from the pipes

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29
Q

Absorption of Pb

A
  • Similar to Ca++
  • A large uptake of Ca++ can absorb lead more efficiently in GI tract
  • Growing children absorb 50% of ingested lead
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30
Q

Distribution of Pb

A
  • Similar to Ca++
  • Primarily stored in bones and teeth (half life 20 years)
  • Bound in red blood cells (half life 25 years)
  • Stored in muscle (half life 40 days)
  • Crosses blood brain and placental barriers (half life 2 years)
31
Q

Neurotoxicity

A
  • Pb mimic Ca++
  • High doses enough to trigger apoptosis and necrosis
  • Low doses interfere with all sorts of neuronal functions
  • Pb++ dampens the electrochemical signal, fewer neurotransmitters are released
32
Q

High doses enough to trigger apoptosis and necrosis

A
  • High intracellular Ca++
  • Inhibits ATP production
  • Inhibits superoxide dismutase activity, exacerbating ROS generation
33
Q

Low doses interfere with all sorts of neuronal functions

A
  • Inhibits neurotransmission between neurons

- Decrease in neuron growth and development in the young

34
Q

Normal neuronal function

A
  • Ca++ movement across the nerve axon, electrochemical transmission of the signal
  • Release of neurotransmitters into the synaptic cleft
35
Q

Heme biosynthesis

A
  • Lead inhibits many steps in heme biosynthesis (especially ALA dehydrogenase and ferrochelatase)
  • can result in anemia
36
Q

Carcinogenicity

A

inorganic Pb probably carcinogenic

37
Q

Manganese gasoline

A
  • used as an additive
  • increase in atmosphere and aquatic Mn2++
  • Neurotoxin
  • New additives are being used even though MMT is used in small amounts
38
Q

Mercury (Hg)

A
  • found in ores

- liquid at room temperature

39
Q

Hg uses

A
  • Readily mixes with other metals (extract silver and gold)
  • Thermometers and other gauges
  • Mercury (tilt) switches
  • Hg Gas in fluorescent lightbulbs
40
Q

Sources of Hg

A
  • Industrial sources: burning coal and pulping paper

- Natural sources: volcanoes

41
Q

Cycling of Hg

A
  • Hg gets oxidized in Hg++ naturally
  • Bacteria take up Hg++, methylate it into methylmerucry
  • MeHg biomagnifies in fish, bigger fish eat smaller fish, we eat top predator
42
Q

Hg accumulation in fish consumption recommendations

A
  • no more than 150g a week

- pregnant no more than 150g per month

43
Q

Mercury Disposition-Mercury liquid and vapour (Hg0)

A
  • vapour absorbed via inhalation
  • liquid barely absorbed in GI tract
  • readily distributed in tissues
  • gets converted to Hg++ enzymatically
44
Q

Mercury Disposition-Mercury salts (Hg+ or Hg++)

A
  • barely absorbed in GI tract

- conjugated to free cysteine and accumulates in the kidney

45
Q

Mercury Disposition-Organic mercury (methyl mercury)

A
  • readily absorbed in GI tract
  • rapidly distributed throughout the body
  • concentrates in the brain
46
Q

Toxic effects-Mercury liquid and vapour (Hg0)

A
  • High doses inhaled can cause acute bronchitis that can be lethal
  • Neurotoxic=tremors, gingivitis, erethism (memory loss, increased excitability, insomnia, depression, shyness)
47
Q

Toxic effects-Mercury salts (Hg+ or Hg++)

A
  • kidney damage leading to kidney failure
  • non-specifically bind to -SH groups on proteins
  • limited neurotoxic effects
48
Q

Toxic effects-Organic mercury (methyl mercury)

A
  • very neurotoxic=paresthesia (numbness), ataxia (lack of coordination muscle movement), blindness
  • children and fetuses are particularly vulnerable
49
Q

Mad Hatter

A

-Hg poisoning

50
Q

Historic Hg poisonings

A
  • Minamata disease
  • Iraq poisoning
  • Ontario Minamata disease
51
Q

Minamata Disease (Japan)

A
  • chemical factory in Japan dumped inorganic mercury salts into the bay
  • converted to MeHg by bacteria
  • biomagnification in fish
52
Q

Symptoms of MeHg poisoning

A
  • central and peripheral nervous system degeneration
  • tingling and numbness of limbs
  • impaired motor function
  • impaired vision and speech
53
Q

Iraq poisoning

A
  • drought and famine
  • grain shipped as aid to be planted was coated in MeHg
  • not labelled in the right language
  • consumed instead of planted
54
Q

Ontario Minamata disease

A
  • first nations communities poisoned by consuming MeHg contaminated fish
  • caused by dumping waste from pulping mills
55
Q

Cell culture effects of MeHg

A
  • ROS generation
  • glutation reduction
  • high intracellular Ca++ levels
  • mitochondrial damage
  • leads to apoptosis or necrosis
56
Q

Ebselen

A

-powerful antioxidant that protects the mitochondria and cells from damage

57
Q

Astrocytes

A
  • surround neurons and hold them in place
  • supply nutrients and oxygen to neurons
  • insulated on neuron from another
  • destroy pathogens and remove dead neurons
58
Q

MeHg inhibits membrane ion transporters..

A
  • inhibits the ability of the astrocytes to ion regulate

- causes them to swell and burst

59
Q

Hg used to treat syphilis

A
  • passed from the americas to europe
  • cure was mercury ointments, injections, breathing Hg0 vapours, and sweat baths
  • forced to drink Hg
  • excessive saliva, frothing at the mouth
60
Q

Arsenic (As)

A
  • valence states
  • 3+ most toxic
  • conjugated with other elements
61
Q

As-natural environmental contaminant

A
  • exposed through drinking water

- max of 10 ppb

62
Q

As-current uses

A
  • industrial chemical synthesis
  • component of CCA treated wood
  • use as a pesticide
  • used as a poison
63
Q

As poison

A
  • white odourless powder that is undetectable in food

- symptoms resemble food poisoning, dysentery, cholera

64
Q

As disposition

A
  • salts readily absorbed because they resemble phosphate
  • methylated in liver to methyl-As which is not as toxic as free As
  • Methyl-As excreted by kidneys
65
Q

Acute As effects

A
  • Mitochondrial respiration poisoning
  • resemble phosphate ions, compete for binding at ATP synthase
  • inhibits pyruvate dehydrogenase
  • death from cardiovascular failure due to insufficient ATP
  • replaces S in thiol groups and inhibits protein functions
  • necrosis of GI tract leading to internal bleeding
66
Q

Chronic As effects

A
  • liver injury
  • cardiovascular disease
  • neurological disorders, impaired cognitive development in children
67
Q

As-carcinogenic

A
  • fatal skin cancers are the most common mode of lethality

- Cancers of liver, lung, bladder

68
Q

Biotransformation of As

A
  • generates ROS

- damages DNA in two ways: direct strand breakage, oxidizing guanine base pairs to form 8-hydroxyguanin

69
Q

Epigenetic factors

A
  • control whether genes are expressed or not independent of the genetic code
  • dependant on SAM to donate a methyl group to methylate DNA, effects gene expression
  • alters the epigenetic regulation of genes
70
Q

As-gold mine contaminant

A
  • used to dump mine tailings on the grounds, As to the waterways
  • deaths from eating snow with As in it
  • started storing in underground tundra
  • climate change melting the tundra
  • economic externally
71
Q

Copper (Cu)

A

-exposed to humans by good, beverages, and drinking water

72
Q

Toxicity Cu

A
  • produced in industrial and mining activities
  • common pollutant in aquatic systems
  • toxic to aquatic animals
73
Q

Cu toxicity in fish

A
  • acutely lethal for fish, low LC50
  • dramatic sub-lethal effects
  • impairs olfactory in fish

Toxicology (14 decks)

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