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Metal Toxicity Flashcards

(73 cards)

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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
Batteries
88% of all lead now used is in batteries
26
Pb Ammunition
- banned in lots of place | - can lead to toxic effects and accumulate in wildlife
27
Flint water crisis
- 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
28
Corrosion control of lead
-use orthophosphates to reduce the amount of lead leaching in from the pipes
29
Absorption of Pb
- Similar to Ca++ - A large uptake of Ca++ can absorb lead more efficiently in GI tract - Growing children absorb 50% of ingested lead
30
Distribution of Pb
- 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
Neurotoxicity
- 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
High doses enough to trigger apoptosis and necrosis
- High intracellular Ca++ - Inhibits ATP production - Inhibits superoxide dismutase activity, exacerbating ROS generation
33
Low doses interfere with all sorts of neuronal functions
- Inhibits neurotransmission between neurons | - Decrease in neuron growth and development in the young
34
Normal neuronal function
- Ca++ movement across the nerve axon, electrochemical transmission of the signal - Release of neurotransmitters into the synaptic cleft
35
Heme biosynthesis
- Lead inhibits many steps in heme biosynthesis (especially ALA dehydrogenase and ferrochelatase) - can result in anemia
36
Carcinogenicity
inorganic Pb probably carcinogenic
37
Manganese gasoline
- 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
Mercury (Hg)
- found in ores | - liquid at room temperature
39
Hg uses
- Readily mixes with other metals (extract silver and gold) - Thermometers and other gauges - Mercury (tilt) switches - Hg Gas in fluorescent lightbulbs
40
Sources of Hg
- Industrial sources: burning coal and pulping paper | - Natural sources: volcanoes
41
Cycling of Hg
- 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
Hg accumulation in fish consumption recommendations
- no more than 150g a week | - pregnant no more than 150g per month
43
Mercury Disposition-Mercury liquid and vapour (Hg0)
- vapour absorbed via inhalation - liquid barely absorbed in GI tract - readily distributed in tissues - gets converted to Hg++ enzymatically
44
Mercury Disposition-Mercury salts (Hg+ or Hg++)
- barely absorbed in GI tract | - conjugated to free cysteine and accumulates in the kidney
45
Mercury Disposition-Organic mercury (methyl mercury)
- readily absorbed in GI tract - rapidly distributed throughout the body - concentrates in the brain
46
Toxic effects-Mercury liquid and vapour (Hg0)
- High doses inhaled can cause acute bronchitis that can be lethal - Neurotoxic=tremors, gingivitis, erethism (memory loss, increased excitability, insomnia, depression, shyness)
47
Toxic effects-Mercury salts (Hg+ or Hg++)
- kidney damage leading to kidney failure - non-specifically bind to -SH groups on proteins - limited neurotoxic effects
48
Toxic effects-Organic mercury (methyl mercury)
- very neurotoxic=paresthesia (numbness), ataxia (lack of coordination muscle movement), blindness - children and fetuses are particularly vulnerable
49
Mad Hatter
-Hg poisoning
50
Historic Hg poisonings
- Minamata disease - Iraq poisoning - Ontario Minamata disease
51
Minamata Disease (Japan)
- chemical factory in Japan dumped inorganic mercury salts into the bay - converted to MeHg by bacteria - biomagnification in fish
52
Symptoms of MeHg poisoning
- central and peripheral nervous system degeneration - tingling and numbness of limbs - impaired motor function - impaired vision and speech
53
Iraq poisoning
- 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
Ontario Minamata disease
- first nations communities poisoned by consuming MeHg contaminated fish - caused by dumping waste from pulping mills
55
Cell culture effects of MeHg
- ROS generation - glutation reduction - high intracellular Ca++ levels - mitochondrial damage - leads to apoptosis or necrosis
56
Ebselen
-powerful antioxidant that protects the mitochondria and cells from damage
57
Astrocytes
- 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
MeHg inhibits membrane ion transporters..
- inhibits the ability of the astrocytes to ion regulate | - causes them to swell and burst
59
Hg used to treat syphilis
- 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
Arsenic (As)
- valence states - 3+ most toxic - conjugated with other elements
61
As-natural environmental contaminant
- exposed through drinking water | - max of 10 ppb
62
As-current uses
- industrial chemical synthesis - component of CCA treated wood - use as a pesticide - used as a poison
63
As poison
- white odourless powder that is undetectable in food | - symptoms resemble food poisoning, dysentery, cholera
64
As disposition
- 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
Acute As effects
- 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
Chronic As effects
- liver injury - cardiovascular disease - neurological disorders, impaired cognitive development in children
67
As-carcinogenic
- fatal skin cancers are the most common mode of lethality | - Cancers of liver, lung, bladder
68
Biotransformation of As
- generates ROS | - damages DNA in two ways: direct strand breakage, oxidizing guanine base pairs to form 8-hydroxyguanin
69
Epigenetic factors
- 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
As-gold mine contaminant
- 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
Copper (Cu)
-exposed to humans by good, beverages, and drinking water
72
Toxicity Cu
- produced in industrial and mining activities - common pollutant in aquatic systems - toxic to aquatic animals
73
Cu toxicity in fish
- acutely lethal for fish, low LC50 - dramatic sub-lethal effects - impairs olfactory in fish

Toxicology (14 decks)

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