Toxicology

Question 1

What is poison?

Answer 1

any substance which, if taken into/formed in the body, destroys life or impairs health

Question 2

What are the 5 types of poison?

Answer 2

1) Corrosives: Powerful chemicals that destroy tissues
2) Irritants: Ingested - irritant to gut, causing nausea & diarrhoea
3) Systemic poisons: Attacks a certain biochemical systems (e.g. CO binds to haemoglobin)
4) Toxins: Poisons produced by living organisms
5) Venoms: Poisons delivered by bites & stings

Question 3

How is carbon monoxide produced?

Answer 3

Comes from partial combustion of fuel/other organic material

Question 4

How is CO poisonous? (2)

Answer 4

1) 4 Haem units in each haemoglobin protein = each unit is an iron atom held together by 4 nitrogen atoms. Haem unit picks up oxygen molecule; oxygen binds to iron
2) The iron atom binds to CO more strongly than O2. CO blocks the site on the iron and prevents O2 from being taken up, forming carboxyhaemoglobin irreversibly

Question 5

How is carbon dioxide poisonous?

Answer 5

if present in high concentration, can lead to asphyxiation

Question 6

How does our body react to venom if ingested?

Answer 6

Since venom is a protein, it will be rapidly broken down into amino acids by enzymes in the digestive system

Question 7

What is the difference between poison and remedy?

Answer 7

anything can be poison, depending on dose

Question 8

How do we measure toxicity?

Answer 8

LD50: Amount needed to kill half a given population of test animals. Quoted in terms of weight of poison per unit body weight

Question 9

What are 5 factors that affect the dose needed to poison someone?

Answer 9

1) Size: larger doses for larger bodies
2) Age: metabolism changes with age
3) State of health: especially condition of the liver
4) History: build up/loss of tolerance. If one’s body is accustomed to a toxin, it will take a higher dose to kill him
5) Paradoxical reactions: opposite of what is expected (rare but known)

Question 10

What are the 3 conditions needed for poison to work?

Answer 10

1) absorption into the body
2) reach the target organ
3) build up in the target organ before excretion (rate of build up must be > rate of excretion)

Question 11

What are 4 routes of poison administration?

Answer 11

1) Oral administration: absorbed through digestive tract
2) Intravenous (injection): directly into blood stream. Efficient
3) Inhalation: rapidly from lungs to blood
4) Through mucus membranes: often fast & efficient

Question 12

How does the stomach & small intestine work with/against poison?

Answer 12

The stomach and small intestine processes proteins to peptides & amino acid saccharides for absorption. Sometimes, the body can break down poison into harmless substances. Hence, if not absorbed, the poison will not be effective.

Question 13

How does the liver work against poison?

Answer 13

Anything absorbed from the intestine will be flowed to the liver for detox (chemical transformations). The liver can make toxic products non toxic, where it can be easily excreted

Question 14

Why is poison delivered by breathing more potent than ingestion?

Answer 14

Blood flow: intestine -> liver -> lungs
Lungs come after the liver in blood flow. Hence, whatever enters the lungs goes straight into bloodstream before it enters the liver

Question 15

What are xenobiotics?

Answer 15

Molecules that the body recognises as “strange”, not naturally produced by the body & not supposed to be there

Question 16

What are the 3 ways the body deals with xenobiotics?

Answer 16

1) Accumulate: e.g. lead or Strontium in bones
2) Excrete: Arsenic or Thallium in hair (not in the body)
3) Transform: increase solubility to be excreted (liver’s job)

Question 17

What is the biological effect of alcohol?

Answer 17

depresses the central nervous system

Question 18

How is alcohol distributed in the body?

Answer 18

At first, it is absorbed by stomach (20%) and small intestine (80%). It appears in the blood in minutes; complete in 30-60min. Blood will distribute alcohol uniformly throughout the body, except bones, fat and hair

Question 19

What are 3 ways to measure alcohol concentration level in one’s body?

Answer 19

1) Measure blood alcohol = concentration in the brain (Gas chromatography)
2) Measure breath alcohol (measured by police on roadside)
3) Post mortem: blood, urine, vitreous humour

Question 20

How is alcohol eliminated from the body? (2)

Answer 20

1) 2-5% is lost through kidneys (urine) & lungs (breath)
2) Most of ethanol will be converted into acetaldehyde by alcohol dehydrogenase (an enzyme in liver & small intestine. It will further oxidise into acetic acid by aldehyde dehydrogenase (liver). Acetic acid can be handled by the body (part of our normal metabolism). Further broken down into CO2, which is exhaled

Question 21

What is the alcohol limit in Singapore? (2)

Answer 21

35 mg of alcohol per 100 ml of breath, or 80 mg of alcohol per 100 ml of blood.

Question 22

How do we calculate blood alcohol level?

Answer 22

c = a/pr
c = maximum concentration (g/1000ml)
a = amount of alcohol taken (g)
p = person’s weight (kg)
r = widmark factor

Question 23

What is the Widmark factor (r)? What is the factor for men and women?

Answer 23

Proportion of total body mass over the body mass which the alcohol can be distributed.
men: 0.68
women: 0.55 (due to higher proportion of fatty tissue, which cannot absorb alcohol)

Question 24

What is Henry’s law?

Answer 24

For solutions at low concentrations, the vapour pressure of the solute is proportional to its mole fraction. More alcohol dissolved in blood = proportionately more alcohol in breath

Question 25

What is the ratio for alcohol in blood to breath?

Answer 25

2300:1

Question 26

How does a breathalyser work? (5)

Answer 26

1) Contains potassium dichromate & sulfuric acid
2) Ethanol reacts with potassium dichromate (orange)
3) Becomes oxidised & chromium is reduced, becoming chromium sulfate (green)
4) Since orange of K2Cr2O7 corresponds to absorbing light at 420nm, we are measuring the loss of absorbance at 420nm
5) Corresponds to alcohol level in breath (in turn, alcohol level in blood)

Question 27

How can we back calculate the alcohol level from time of test to time of incident?

Answer 27

Knowing how fast the body eliminates alcohol.

Time of test = Time of incident - hours x B

1) Finding lowest likely elimination rate. B = 12.5 mg of ethanol per 100 ml of blood per hour
2) Finding the highest likely elimination rate. B = 25 mg of ethanol per 100 ml of blood per hour

Question 28

What are inorganic poisons?

Answer 28

Elements that may neither be created nor destroyed. Can be present in different compounds, but toxicity is tied to the element

Question 29

What are some examples of inorganic poisons?

Answer 29

Arsenic, antimony, mercury, thallium

Question 30

What is an advantage when it comes to detecting inorganic poisons?

Answer 30

The element will still be detectable after death, burial and even after cremation

Question 31

Why was arsenic a popular choice of poison? (3)

Answer 31

1) readily found in medicines in pharmacies, was an FDA approved leukemia medicine
2) found in fly paper (to trap flies)
3) lacks obvious symptoms

Question 32

How does the Marsh test work?

Answer 32

1) Relies on the fact that if you have arsenic in any form, it can be converted into arsine (AsH3)
2) Treat sample with zinc powder and hydrochloric acid. Forms AsH3, a gas
3) AsH3 flows along tube and is heated, becomes decomposed into Arsenic metal (deposited on the glass)
4) There are only 2 elements in the periodic table that shows this behaviour. The other compound is less stable and will deposit itself on another part of the apparatus

Question 33

What were the benefits of using the Marsh test for Arsenic?

Answer 33

Highly quantitative and specific

Question 34

Now, what do we use in place of the Marsh test for Arsenic?

Answer 34

Atomic Absorption Spectrometer (AAS)

Question 35

How does neurotransmission work? (5)

Answer 35

1) When the nerve cell is in resting state, there will be more K+ than Na+ inside, causing the cell to have a slight negative voltage (–85mV)
2) Nerve signal is transmitted from one cell to another through chemical signal. When signal comes down the line, neuron is excited. Sodium channels open and sodium floods in. Voltage changes to +30mV
3) Neurotransmitter (acetyl choline) is released, exciting the next neuron
4) Potassium channels open and potassium flows out. Neurotransmitter returns/is destroyed by an enzyme
5) Ion pumps redistribute Na+ and K+. Neuron restored to original state

Question 36

Describe Sarin’s Mechanism of Action.

Answer 36

1) Sarin inhibits acetyl cholinesterase. Body cannot control amount of neurotransmitters
2) Excess neurotransmitter is present
3) Continued nerve stimulation. Twitching, convulsions, then death.
Often starts with blindness due to effect on eye nerves & muscles

Question 37

What is Sarin’s Antidote?

Answer 37

Atropine: inhibits action of acetylcholine. Is still toxic. Acts in the opposite biochemical effect of Sarin, and hence cancels out the effect of Sarin

Question 38

What is Thallium? How does it work?

Answer 38

Thallium sulfate (Tl2SO4)is formerly widely available as rat poison. At a lethal dose of 12mg/kg, it interferes with the nervous system due to similarity with potassium

Question 39

Why is Barium poisonous, but not BaSO4 when ingested?

Answer 39

BaSO4 is insoluble. Hence, it cannot be absorbed and cannot reach its target organ.