8. metal toxicology (As)

Question 1

arsenic is what kind of metal

Answer 1

light metal

Many valence states (+3 and +5 most common, +3 being the most toxic). Usually conjugated with other elements.

Question 2

As is usually a natural environmental contaminant and most are exposed through

Answer 2

drinking water sources
-World Health Organization (WHO) recommends a maximum of 10 ppb of As in drinking water.
Some areas in California are over 50 ppb.
In Bangladesh, whole areas are well over 150 ppb.

Question 3

Classic dermatitis

Answer 3

caused by chronic exposure to As (but most often on feet and hands)

Question 4

Arsenic doesn’t have many uses anymore

Answer 4

1. Some industrial chemical synthesis uses
2. A component of CCA (Copper, cadmium and arsenic) treated wood.
   - Not commonly used anymore
3. Older use as a pesticide
4. Often used as a poison (Arsenic trioxide)
   - White odorless powder that is undetectable in food while eating it. Symptoms of poisoning resemble food poisoning, dysentery and cholera

Question 5

Disposition

Answer 5

• Arsenic salts readily absorbed because they
  resemble phosphate (PO4-)
• Gets methylated in liver to methyl-As, which is not as toxic as free As
• Methyl-As excreted by kidneys

Question 6

Arsenic toxic effects

Acute

Answer 6

• Mitochondrial respiration poisoning
• AsO4-3 resemble phosphate ions, and compete for
binding at ATP synthase. Also inhibits pyruvate
dehydrogenase (entry into the TCA cycle)
• Death from cardiovascular failure due to insufficient ATP
• AsO3-3 replaces S in thiol groups and inhibits protein
functions
• Also necrosis of GI tract leading to internal bleeding

Question 7

Arsenic toxic effects

Chronic

Answer 7

• Liver injury
• Cardiovascular disease
• Neurological disorders and impaired cognitive
development in children

Question 8

Carcinogenic

Answer 8

• Fatal skin cancers are the most common mode of lethality for chronic As poisoning
• Also cancers of liver, lung, bladder

Question 9

The biotransformation of arsenic generates ROS, which can damage DNA in two ways:

Answer 9

a. ) direct strand breakage

b. ) oxidizing guanine base pairs to form 8-hydroxyguanine

Question 10

‘Epigenetic’ factors

Answer 10

control whether genes are expressed or not independent of the genetic code. Many are dependent on S-adenosyl methionine (SAM) to donate a methyl group to methylate DNA and other molecules that affect gene expression. Methylation of As may deplete the SAM pool, which thus alters the epigenetic regulation of genes that are important in the progression of carcinogenesis.

Question 11

Arsenic is a major contaminant of gold mining

Answer 11

• The `Giant Mine’ is 5 km north of Yellowknife. Produced 7 million ounces of gold from 1948 to 2004.
• They used to just dump the mine tailings on the ground, As2O4 leaked into waterways.
• In 1951 a child from a local First Nation community died from eating snow that had As contamination.
• The mining company started collecting the As2O4 and storing it underground in the frozen tundra.
• The owners of the mine left the mine to the Government of Canada in 2004…
• There is 234 million kg of As2O4 stored at this site, and climate change is melting the tundra that is keeping it in place.
• Projected cost to cleanup the site: $900 million to $1 billion of taxpayer dollars. Another example of an economic externality… Sigh… Let’s get ethical again….