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toxicology > 8. metal toxicology (Pb) > Flashcards

8. metal toxicology (Pb) Flashcards

1
Q

Major toxic metals

A 
Arsenic (As)
Cadmium (Cd)
Mercury (Hg)
Nickel (Ni)
Lead (Pb)
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2
Q

Essential metals

A 
Iron (Fe)
 Copper (Cu)
 Zinc (Zn)
 Selenium (Se)
 Cobalt (Co)
 Molybdenum (Mo) 
 Magnesium (Mg) 
 Manganese (Mn)
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3
Q

Metals used in medicine

A

Aluminum (Al)

Lithium (Li) Gold (Au) Platinum (Pt)

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4
Q

Metals

A

are naturally occurring elements that can be introduced to humans and the environment through industrial, agricultural, medical, and “technological” activities

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5
Q

metals are defined by?

A 
Defined by the physical properties of the element in a solid state
– High luster (reflectivity)
– High electrical conductivity
– High thermal conductivity
– Mechanical ductility and strength
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6
Q

how do metals differ from many toxicants?

A

Differ from many toxicants because most are natural and do not quickly break down in the body or environment.
– Many are essential for cell function too (i.e., Zn)

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7
Q

In a toxicology context, can exert toxic effects:

A

– Inhibit critical enzyme function.
– Can lose or gain 1 or more electrons and form highly reactive cations – contributes to oxidative damage.
– Can also replace other metals by binding to molecular targets.
• Cd, Cu and Ni can replace Zn in some physiological processes

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8
Q

• Bismuth subsalicylate

A

– Increase water absorption in the intestines – Can kill bacteria that cause diarrhea
– Antacid
– Can cause black stool and black tongue
– And can interact with various drugs…

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9
Q

Major toxic metals

A

(e.g., Pb, Cd)

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10
Q

Essential metals

A

(e.g., Zn, Cu)

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11
Q

Medicinal metals

A

platinum and bismuth

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12
Q

Minor toxic metals from technology

A

indium, uranium

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13
Q

Toxic metalloids

A

As,antimony

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14
Q

Non metallic elemental toxicants

A

Se, fluoride

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15
Q

As always, the route of exposure, dose, and duration and frequency of exposure are critical factors that determine the relative toxicity.
• Additionally, other factors contribute to metal toxicity such as:

A

– Age - Younger and older individuals more sensitive to metal toxicity
• Children can absorb some metals in the GI tract better (e.g., Pb)
– Sex – However, not always clear as to why and may be linked to lifestyle, location, etc.
– Genetics(i.e.,Adaptivegenotypes)
• Adaptationsmayincludeanincreasedcapacityfor biotransformation, reduced absorption, increased excretion
– Any part of the toxicant disposition really

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16
Q

Different types of proteins influence the disposition in the body

A

1) Non-specific binding to proteins
2) Metallothioneins
3) Transferrin
4) Ferritin

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17
Q

1) Non-specific binding to proteins

A

(i.e., albumin and hemoglobin), that can move metals throughout the body

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18
Q

2) Metallothioneins

A

are specific metal-binding proteins.
– High affinity for Zn, Cd, Cu, Hg
– Can protect the cell from oxidative damage by binding to the metals to prevent them from doing their thing.

19
Q

3) Transferrin

A

binds to Fe in the plasma to help transport it across cell membranes.
– Ceruloplasmin will convert Fe to the right form to bind to transferrin.

20
Q

4) Ferritin

A

is a primary cellular storage site for Fe.
– Can sequester Fe in the cell if necessary (bacterial infection!)
– But also binds Cd, Zn, beryllium, Al

21
Q

Platinum compounds

A

effective for cancer chemotherapy – Also gallium and titanium compounds can be used.

22
Q

Al can be used in

A

antacids (i.e., Aluminum hydroxide)

23
Q

Au can be used in treating

A

rheumatoid arthritis.

– “gold salts”

24
Q

Lithium used for

A

bipolar disorder.

25
Q

Lead

A

found in ores with other metals. It can be mined for, but is often a byproduct of smelting other metals.
It’s dense and malleable, and is the heaviest non-radioactive metal.

26
Q

Pb used as a malleable metal since…

A

Used as a malleable metal since 6500 BC in Turkey

27
Q

The Romans used a lot of Pb to make all their

A

plumbing and much of their dishware. They even added powdered Pb to wine as a sweetener.

28
Q

Kohl

A

is a mixture of lead sulfide and other resins that is used as a mascara developed in Egypt ~3100 BC.
– It is still used today in some cultures… but not all preparations have Pb in them.

29
Q

gasoline

A 
A lot of lead was used in gasoline
Tetraethyl lead (TEL)
 – Very early automobiles used ethanol as an anti-knocking agent in gasoline. This was not patentable though, and the corporations wanted to make \$\$$.
30
Q

Thomas Midgley

A

was working for General Motors and showed that tetraethyl lead (TEL) could replace ethanol in this function. This was patented.
– DuPont chemical owned 30% of GM and made the compound.
– They just named it ‘ethyl’ because the public already knew about lead toxicity.
• By 1936, 90% of all gasoline sold had TEL in it.
• In 1972 the Environmental Protection Agency indicated that TEL was to be phased out of gasoline. Ethyl corporation promptly sued, but lost.
• 1979 a seminal paper was published that showed that even low doses of lead caused developmental defects (lower IQ ratings) in exposed children. Even still… it took until 1982 to completely ban it…

31
Q

Exposure to Pb in utero and in childhood can

A

lower IQ due to neurotoxicity.
It’s speculated that younger populations now are a few IQ points ‘smarter’ than us
older distinguished folks.
Also speculated that the drop in Pb led to a drop in crime rates due to less antisocial behaviour.
Since the phase out, Pb in the air has decreased

32
Q

Other sources of Pb that we still encounter

A
  1. Old paint
  2. Old piping
  3. Batteries
  4. Glass and ceramics
  5. Ammunition
  6. Solder (electronics)
  7. Soil and food (principle exposure source)
33
Q

Old paint

A
  • Lead was added to oil paints up until the 1970s (10 to 50%)
  • Canada Hazardous Products Act (1976) reduced to max. 5000 mg/kg (0.5%)
  • In 2010, this was reduced to 0.009%
34
Q

Old piping

A
  • Lead was used as pipes and as solder joints for brass piping
  • Lead pipes phased out in the 1950s, lead solder joints in 1989
  • Winnipeg uses orthophosphate in its water supply to decrease Pb levels
35
Q

Batteries

A

• 88% of all lead now used is in batteries

36
Q

however Pb from ammunition (and fishing tackle) can lead to

A

toxic effects and accumulate in wildlife.

37
Q

Absorption

A
  • Because Pb2+ is similar to calcium (Ca2+), anybody who is taking up a lot of calcium can absorb lead more efficiently in the GI tract
  • Growing children absorb 50% of ingested lead (because they are growing bones and such)
  • Adults who are well nourished w/ sufficient Ca only take up 10% and retain 5%
38
Q

Distribution

A

• Again because of Ca+2 similarities, Pb is primarily stored in bones and teeth (half life 20 years)
• We can test our teeth to estimate our Pb exposure we had as children
• Pb is bound in red blood cells (half life 25 days)
• Can be stored in muscle (half life 40 days)
• Readily crosses the blood brain and placental barriers (2 year half life in
brain)

39
Q

Neurotoxicity

A

Mostly based upon the ability of Pb+2 to mimic Ca+2
High doses enough to trigger apoptosis and necrosis in neuronal cells
- Triggers the ‘high intracellular Ca+2’ response
- Inhibits ATP production in the mitochondria
- Actually inhibits superoxide dismutase activity, exacerbating any ROS
generation
Low doses can generally interfere with all sorts of neuronal functions
- Inhibits neurotransmission between neurons
- Decrease in neuron growth and development in the young

40
Q

Normal neuronal function:

A
  1. Ca+2 movement across the nerve axon is part of the electrochemical transmission of the signal
  2. This causes a release of neurotransmitters into the synaptic cleft to propagate the signal to the next neuron
41
Q

Internal Pb2+ dampens the

A

electrochemical signal, and fewer neurotransmitters are released

42
Q

Heme biosynthesis

A

• Lead inhibits many steps in heme biosynthesis (especially ALA dehydrogenase
and ferrochelatase)
• Thus can result in anemia (insufficient functioning red blood cells to carry O2)

43
Q

Carcinogenicity

A

Inorganic Pb compounds were recently reclassified in 2006 as probably carcinogenic to humans.

44
Q

The compound Manganese (Mn2+)

A

was then used as an additive to gasoline.
• Actually, Methylcyclopentadienyl manganese tricarbonyl (MMT) is added
– Produced by the company Afton Chemical Corporation (Afton), formerly known as the Ethyl Corporation…
– This led to increases in atmospheric Mn2+ and Mn2+ in our aquatic systems, it is a known neurotoxin…
– Now new additives are being used even though MMT is still used in small amounts.
• I wonder if the new alternatives are harmless to people and the environment?

toxicology (10 decks)

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