8. metal toxicology (Hg)

Question 1

Mercury

Answer 1

is also found in ores, but is rare (only 4 major mines world wide).
It is liquid at room temperature… why it was named after the Roman god of swiftness.

Question 2

Hg Toxicity

Answer 2

1. Readily mixes with other
metals (to form amalgams)
2. Thermometers and other gauges
3. Mercury (tilt) switches
4. Hg gas in fluorescent lightbulbs

Question 3

1. Readily mixes with other

metals (to form amalgams)

Answer 3

• Mixed with silver for dental
fillings
• Used to extract gold and silver
from ore
• Still used today by ‘artisanal
miners’ who produce 25% of global gold

Question 4

Main industrial sources:

Answer 4

Burning coal and pulping paper

Question 5

Natural sources

Answer 5

Volcanoes
Hg0 gets oxidized into Hg2+ naturally.
Bacteria in sediment take up Hg2+ and can methylate it into methylmercury (MeHg)
i.e., MeHg bioaccumulates in fish, bigger fish eat the smaller fish, we eat the bigger top predator fish (e.g., tuna)

Question 6

Health Canada recommendations for “fish” consumption:

Answer 6

No more than 150 g per week of top predator fish (tuna, shark, swordfish, etc.).
Pregnant women no more than 150 g per month. - A can of tuna can be up to~120g…
Solid white tuna has three times the Hg levels of light tuna

Question 7

Mercury disposition

Answer 7

• Mercury liquid and vapor (H0)
• Mercury salts (Hg1+ and Hg2+)
• Organic mercury (methylmercury)

Question 8

Mercury liquid and vapor (H0) disposition

Answer 8

• Vapor absorbed via inhalation (80% inhaled)
• Liquid barely absorbed in GI tract
• Readily distributed in tissues
• Gets converted to Hg2+ enzymatically

Question 9

Mercury salts (Hg1+ and Hg2+) disposition

Answer 9

• Barely absorbed in GI tract (10%)

- Gets conjugated to free cysteine and accumulates in the kidney

Question 10

Organic mercury (methylmercury) disposition

Answer 10

• Readily absorbed in GI tract
• Rapidly distributed throughout body… concentrates in brain (10% of
  absorbed)

Question 11

Mercury liquid and vapor (H0) toxic effects

Answer 11

• High doses inhaled can cause acute bronchitis that can be lethal
• Neurotoxic: causes tremors, gingivitis, and erethism (memory
  loss, increased excitability, insomnia, depression, and shyness)

Question 12

Mercury salts (Hg+1 and Hg+2) toxic effects

Answer 12

• Mostly kidney damage leading to kidney failure in high doses
• Can non-specifically bind to –SH groups on proteins
• Limited neurotoxic effects

Question 13

Organic mercury (methylmercury and dimethylmercury) toxic effects

Answer 13

• Very neurotoxic. Causes paresthesia (numbness), ataxia (lack of coordinating muscle movement), blindness
• Like Pb, children and fetuses are particularly vulnerable

Question 14

Minamata disease

Answer 14

Chemical factory in Japan dumped inorganic mercury salts into the bay.
Converted to MeHg by bacteria, bioaccumulated by fish.
The Minamata residents, as common in Japan, eat a lot of fish!
Because folks didn’t yet understand the conversion to MeHg, originally thought it was a new disease.

Question 15

Minamata disease symptoms

Answer 15

• Central and peripheral nervous system degeneration
• Tingling and numbness of limbs - Impaired motor function
• Impaired vision and speech

Question 16

Iraq poisoning

Answer 16

• Iraq in 1971 was undergoing drought and famine.
• Grain shipped as aid to be planted was coated in methylmercury to prevent fungal growth… colored with pink dye to show toxicity.
• Not labelled in the right language though… it was consumed instead of being planted.
• 6,530 patients were admitted to hospital with poisoning, and 459 deaths were reported.

Question 17

Ontario Minamata disease

Answer 17

• First Nations communities were poisoned by consuming methylmercury contaminated fish in the late 1960s (2 communities in Dryden)
• Mercury contamination was from waste dumping from pulping mills. Over 9000 kg of mercury from 1962 to 1970!

Question 18

Hg poisoning is the basis of ‘Mad as a Hatter’

Answer 18

Lewis Carroll’s “Alice’s Adventures in Wonderland,” published in 1866, contained a character, the Mad Hatter, based on the common stereotype of a slightly demented hat maker.
‘Hatters’ would use mercury salts when making beaver-felt hats and experienced chronic mercury poisoning.

Question 19

How does MeHg cause neurotoxicity?

Answer 19

Not fully clear yet.
We know that in cell cultures, MeHg causes ROS generation, glutathione reduction, and high intracellular Ca2+ levels, and mitochondrial damage. All of this leads to apoptosis and necrosis of nerve cells.

Question 20

Ebselen

Answer 20

powerful antioxidant that protects the mitochondria and cells from damage.

Question 21

Astrocytes are particularly targeted.

Answer 21

surround neurons and hold them in place

supply nutrients and oxygen to neurons insulate one neuron from another destroy pathogens and remove dead neurons

Question 22

MeHg inhibits membrane ion transporters

Answer 22

thus the ability of the astrocytes to ion regulate. This causes them to swell and burst.

Question 23

Mercury used to be used to treat syphilis

Answer 23

Syphilis was the only disease that was passed from the Americas to Europe. Europeans had no resistance.
The only ‘cure’ at the time was mercury ointments, injections, breathing Hg0 vapors, and sweatbaths.
They also forced patients to drink it. One of the symptoms is excessive saliva. Thus the expression ‘frothing at the mouth’ crazy… because late stage syphilis messed with your mind.