Professional Documents
Culture Documents
Toxicology
Science of poisons and poisoning
Reasons
Accidental
Environmental
Occupational
Deliberate
2
Toxicology
Use of poisoning to commit murder
Common in the old days
Less common now
Chemicals tightly controlled
3
Corrosives
Strong acids and alkalis
Concentrated
sulfuric acid
Vitriol
GHS symbol for corrosives
4
Malaysia, 2009
Ameneh Bahrami
Before and after
her acid attack
Drastic effects of sulfuric
acid on the human body
Ameneh Bahrami
8
Irritants
Lead, mercury, arsenic
Irritate the gut
Cause nausea or diarrhoea
Other effects after absorption
9
Systemic Poisons
Attack biochemical systems in body
1
Cyanide
Carbon monoxide
10
Systemic Poisons
Affects the nervous system
Strychnine
Morphine
Atropine
11
Systemic Poisons
7
Inorganic poisons
Arsenic
Antimony
Mercury
Thallium
12
Cyanide
Cassava root is
a staple food
Cassava plant
13
Cyanide
Cutting open the cassava root
Plant releases cyanide
Few cases yearly
Cassava root not properly prepared
14
17
Gas-Hemoglobin Complexes
Color of hemoglobin depends
on the molecule bound to iron
Fe-O2 complex
Fe-CO complex
Red
Pink
20
Sources of CO
Partial combustion of fuel
or other organic material
Sources of CO
Burning butane (C4H10) in excess air
C4H10
6.5 O2
4 CO2
5 H2 O
C4H10
5.5 O2
2 CO2
5 H2 O
2 CO
22
Sources of CO
Partial combustion of
hydrocarbon fuels
Improper ventilation
CO concentration can
build up to toxic levels
23
24
Asphyxiation
28
Socrates
(399 BC)
29
Socrates
Convicted of corrupting
the youths of Athens
Encouraged
them to think
Socrates
30
Socrates
Sentenced to death
Poisoning
Hemlock plant extract
Hemlock plant
31
Socrates
Hemlock contains
various alkaloids
Coniine
Coniine
32
Socrates
Symptoms experienced after drinking hemlock
Numbness from feet upwards
Paralysis reached heart and lungs
Died
33
Augustus
34
Augustus
Poisoned by Empress Livia
Suspected that Livia
wanted to poison him
Refused to eat food
prepared for him
Augustus
35
Augustus
Only ate fruits
from his fig tree
Livia injected
poison into figs
Caesar poisoned
after eating fruits
Lakhvinder
Cheema
37
2009
Lakhvinder Cheema
Lakhvir Singh
38
2009
Cheema and his fiance
had leftover curry for dinner
39
2009
Became very ill
Called emergency services
Food poisoning?
Actual poisoning
40
2009
Sent to the hospital
Lakhvinder Cheema died soon after
Questions
1
42
Aconitum ferox
Native to the Himalayas
Used as a poison in India
Lakhvir Singh went to
India to obtain plant
43
Aconitum ferox
Went to Cheemas house
Poisoned his curry
Aconitum ferox
Contains a very complex alkaloid
Shuts down the
nervous system
Brain still working
Pseudaconitine
45
Accidental poisoning
Plants as a cause of poisoning
47
Accidental poisoning
Plants as a cause of poisoning
Wild garlic leaves vs meadow saffron leaves
Look very similar
Wild garlic
49
Accidental poisoning
Meadow saffron
is highly toxic
Meadow saffron
50
Accidental poisoning
Contains colchicine
Anti-cancer
Overdose
leads to death
Colchicine
51
Accidental poisoning
Plants as a cause of poisoning
Wild garlic leaves vs meadow saffron leaves
Potato plants
Potato tubers
52
Accidental poisoning
Potato tuber is harmless
Potato fruits are toxic
Potato fruits
53
Accidental poisoning
Potato fruits are toxic
Contains oxalic acid
Could have serious
effects in children
Oxalic acid
54
Accidental poisoning
Rhubarb
Stems are edible
Leaves are toxic
Rhubarb
55
Toxins
Natural substances produced
by living species (animals)
Attack biochemical systems
56
Box jellyfish
57
Fugu fish
59
Concentrated in
internal organs
Fugu fish
60
Coastal Taipan
62
Cleopatra
Egyptian Queen
Cleopatra
63
Cleopatra
Affair with Julius Caesar
Julius Caesar
64
Cleopatra
Got together
with Mark Antony
Lost the Final War of
the Roman Republic
Mark Antony
65
Cleopatra
Wanted to commit suicide
Wanted to look nice after death
Asp
67
Biological poisons
Responsible for botulism
Clostridium botulinum
68
Botox
Paralyze muscles
Injection in a
localized area
Does not paralyze
vital muscles
Botox treatment
69
Biological poisons
Responsible for anthrax
Weaponized anthrax
available since WWII
Bacillus anthracis
70
Anthrax outbreak
During the 9/11 crisis
Anthrax outbreak
Anthrax letters
72
Anthrax outbreak
Suspicion turned to Bruce Ivins
U.S. Army microbiologist
Had anthrax in his lab
Committed suicide
Bruce Ivins
73
Poisons
Any substance which, if taken into or formed
in the body, destroys life or impairs health.
74
Paracelsus
Philippus Aureolus Theophrastus
von Hohenheim (1493 1541)
Paracelsus
75
Paracelsus
All substances are poisons, there is none which is
not a poison. The right dose differentiates a
poison from a remedy.
Even water
76
Lethal water
Water poisoning
Over 7 litres
Lethal dose
77
78
Jennifer Strange
79
80
Fox glove
81
Fox glove
Poisonous European wild plant
Contains digitalin
Potent heart muscle stimulant
Digitalin
Also used clinically
Failing heart
Give controlled dose of digitalin
Dose-Response
Steepness of the curve
Variable
How to measure toxicity?
84
85
86
Accuracy of LD50
1
87
Accuracy of LD50
1
Accuracy of LD50
Lethal dose for 50 percent
Guidelines
89
Lethal doses
Types of poison
Lethal dose
(g / kg), mice
Sodium cyanide
10 000
Curare/
strychnine
500
Tetrodotoxin
8 20
Cobra neurotoxin
0.3
Tetanus toxin
0.07
Botulism toxin
0.03
Measure dose
per unit body
weight
90
Size
Larger doses for larger bodies (mg/kg)
Age
State of health
History
Tolerance
Paradoxical reactions
Depression
93
95
Mercury
1
Mercury
1
Mercury
1
99
King Charles II
Many hobbies
Interested in chemistry
Lab accident
Poisoned by
mercury vapor
King Charles II
100
Route of Administration
Must reach target organ to be effective
101
Route of Administration
1
Oral administration
Absorbed through digestive tract
102
Route of Administration
1
Oral administration
Intravenous
103
Route of Administration
1
Oral administration
Intravenous
Inhalation
Forensic Toxicology
In
Food, drink, air
Absorption &
desorption of
gases
Detox
Deposited
in hair, nails
Processing &
absorption
Out
Feces, urine,
sweat, exhaled air
105
Snake venom
Complex peptides
107
Forensic Toxicology
Enter bloodstream
after digestion
Liver = detox factory
Get past liver to go to
the rest of the body
108
Forensic Toxicology
Enter bloodstream
after digestion
Liver = detox factory
Get past liver to go to
the rest of the body
109
Forensic Toxicology
Blood flows past the
lungs to rest of body
Membrane around brain
Prevent molecules
from going into brain
110
Xenobiotics
Strange molecules
Pharmaceuticals
Illegal drugs
Natural substances
Other substances
Nicotine, caffeine
Ethanol
111
Xenobiotics
1
Accumulation in body
Excretion
Lead or strontium
in bones
Arsenic or thallium
Deposited in hair or fingernails
Transform
Increase solubility
Excrete
112
Xenobiotics
Caffeine
113
Xenobiotics
Caffeine that is ingested
114
Xenobiotics
Caffeine
Liver wants to remove caffeine
Transform it
115
Alcohol
Most common poison
Controversial
Essential?
Or evil?
116
Alcohol
Show evils of alcohol
Gin
Gin consumption
was enormous
Gin Lane
117
Alcohol
Beer Street
Beer contains
less alcohol
118
Distribution of alcohol
What happens when someone drinks alcohol?
119
Distribution of alcohol
Rate of adsorption depends on
Kind of drink
Stomach contents
Distributed via the cardio-vascular system
120
Effect of alcohol
Depress the Central Nervous System (CNS)
Depress inhibitions
Depress ability to make judgments
Alcohol
1
122
c = a / pr
Max. conc. (g/ 1000 ml)
Usually converted to
mg / 100 ml of blood
Widmark factor
Men: r = 0.68
Women: r = 0.55
123
Scenario
If a man of 70 kg drinks a double whisky, what
is the concentration of alcohol in his blood?
1
A single = 25 cm3
Scenario
c = a / pr
c = 17 / (70 x 0.68)
c = 0.36 g per 1000 ml of blood
c = 0.036 g per 100 ml of blood
c = 36 mg per 100 ml of blood
125
Effect of alcohol
Effect of alcohol on the brain?
Vary according to amount of alcohol
126
Effect of alcohol
Blood alcohol
conc. (mg/100 ml)
Effects
<50
No obvious effect
50 100
100 150
150 200
200 300
Probably coma
>300
>450
127
Elimination of alcohol
Alcohol present in nature
Fermentation of food
Biomechanism for eliminating alcohol from body
128
Elimination of alcohol
Alcohol dehydrogenase
(liver, small intestine)
CH3CHO
Acetaldehyde
C5H5OH
Ethanol
Aldehyde
dehydrogenase
(liver)
CO2
Carbon dioxide
CH3CO2H
Acetic acid
129
Elimination of alcohol
95% - 98% of alcohol consumed end up as CO2
2% - 5% excreted by kidneys and lungs
130
Distribution of alcohol
Uniformly throughout the body
Except parts with low water content
Bones, fat, hair
Distribution of alcohol
Usually measure blood alcohol
Same concentration as in the brain
Gas chromatography
Roadside
Post-mortem
Henrys Law
How is breath alcohol related to blood alcohol?
133
Henrys Law
How is breath alcohol related to blood alcohol?
Blood alcohol to breath alcohol
2300: 1 ratio
Multiply breath alcohol to get blood alcohol
134
Breath alcohol
Measured at roadside
using breathalyzers
Chromium chemistry
Breathalyzer
135
Breath alcohol
K2Cr2O7
2 Cr2(SO4)3
8 H2SO4
3 CH3COOH
3 C2H5OH
2 K2SO4
11 H2O
138
139
Scenario
A man is arrested after driving a car that was
involved in an accident at 3:00 am. Reliable
eye-witnesses confirm that the driver last
drank an alcoholic drink at least 2 hours
earlier. A blood sample taken at 5:00 am
shows a blood alcohol concentration of 70
mg per 100 ml. Was the driver over the limit?
140
Scenario
Length of time between last drink and accident
is enough to assume that alcohol absorption
has ceased
Method 1
Lowest elimination rate
= 12.5 mg ethanol per 100 ml blood per hour
Ct = C0 t
142
Method 1
Ct = C0 t
Ct = blood alcohol conc. at time of measurement
Method 1
Lowest elimination rate
= 12.5 mg ethanol per 100 ml blood per hour
Ct = C0 t
C0 = Ct + t
Method 1
Highest elimination rate
= 25 mg ethanol per 100 ml blood per hour
Ct = C0 t
C0 = Ct + t
Method 2
Lowest elimination rate
12.5 mg ethanol per 100 ml blood per hour
2 hours at 12.5 mg per hour = 25 mg
Add that 25 mg to the 5 am measurement
70 + 25 = 95 mg per 100 ml
146
Method 2
Highest elimination rate
25 mg ethanol per 100 ml blood per hour
2 hours at 25 mg per hour = 50 mg
Methods 1 & 2
Both methods give same conclusion
148
Inorganic poisons
Toxic elements
vs organic poisons
Inorganic poisons
Arsenic, antimony, mercury, thallium
Detectable after death
Detectable after burial
Detectable after cremation
150
Arsenic trioxide
Once readily and
legally available
Fowlers solution
Arsenic trioxide
151
Arsenic trioxide
Flypaper
Paper coated with glue
Arsenic added to glue
Flypaper
152
Arsenic trioxide
FDA (U.S.) approved for use in the
treatment of some kinds of leukemia
Trisenox
153
Arsenic trioxide
Very common poison in the Victorian era
Inheritance powder
154
A lot of money
in 1869
Arsenic poisoning
confused with
liver disease?
And adding
arsenic?
To drug him?
Due to arsenic?
Travelling court
155
Arsenic trioxide
Widespread use of arsenic in poisoning
Reliable method of testing for arsenic?
156
Marsh Test
Forensic use of
testing for arsenic
Developed by James Marsh
Now superseded by AAS
James Marsh
157
Marsh Test
As2O3
6 Zn
2 AsH3
12 HCl
3 H 2O
6 ZnCl2
158
Marsh apparatus
159
Marsh Test
Can confirm presence of arsenic
Can also estimate the amount of arsenic
Marsh Test
Marsh Test very effective and credible in court
Prosecution got better
Defense
Styrian Defence
161
163
Improve health?
Improve complexion?
Blood vessels damaged
Men
Florence
Maybrick
165
Liverpool, 1889
Florence Maybrick
Charged with murdering
her husband with arsenic
Tries the Styrian Defence
167
Liverpool, 1889
Prosecution
Arsenic purchased and soaked from flypapers
Defense
For use as a cosmetic face wash
168
Liverpool, 1889
Prosecution
Arsenic detected in James Maybricks body
Defense
Self-medication
169
Liverpool, 1889
Verdict: guilty
Sentenced to hang
Commuted to 15 years in prison
Died in 1941
170
Maine,
New England
2003
171
172
Daniel Bondeson
committed suicide
28 April
2 May
27 April
174
Church dispute?
Overdose?
175
Thallium
Formerly widely available
Rat poison
Rat poison
176
Thallium
Lethal dose 12 mg / kg
Interferes with nervous system
177
Thallium
Characteristic symptom
Hair will fall out
178
Graham Young
179
1962
Murdered stepmother
when he was age 14
Sent to Broadmoor
Psychiatric Hospital
Detained and treated
Graham Young
180
1971
Released from hospital
Worked in a warehouse
Poisoned the tea
of his co-workers
Tea
181
Graham Young
Used low doses of thallium or antimony
8 fell ill; 2 died
Bob Egle
Fred Biggs
Cremated
Death triggered investigation
182
Graham Young
Bob Egle
Cremated
Thallium cannot be destroyed
Thallium present in ashes
Life in prison
183
184
Poisoning
Arsenic and thallium
Barium poisoning
Very uncommon
Few people have access
to barium compounds
186
Marie Robards
Poisoned her father
with barium acetate
Father died
No foul play suspected
Marie Robards
187
Marie Robards
Went to University
Studied the play Hamlet
Confessed to a friend
188
Investigation
Victim exhumed
Presence of barium in his body
Marie Robards convicted
Barium was stolen from school chemistry lab
189
Use of Barium
Medical X-rays
190
Barium meal
Contains Barium
Show up digestive
system on X-rays
Barium meal
Why doesnt it poison the patient?
Sarin
Discovered
in
Germany in 1938
Stockpiled by Hitler
Never used in WWII
CH3P(O)(F)OCH(CH3)2
193
March 1988
Used by Iraqi military against Kurdish villagers
Stops nervous system
Causes death
Neurotransmission
How do nerve agents work?
Interfere with biochemical mechanism
196
199
Acetyl
cholinesterase
Acetyl choline
Choline
Inactive
200
201
The Rock
Renegade soldiers steals
chemical weapons
Hero exposed to nerve gas
Injected himself
with antidote
The Rock
202
Atropine
Antidote to Sarin
Opposite effect of Sarin
Atropine
Toxic if not taken as antidote
Inhibits action of neurotransmitter
204
Atropine
Natural compound from
Atropa belladonna
Atropa belladonna
205
Atropine
Atropine dilates the pupils
Beautiful
Used in optometry
Atropa belladonna
206
Poisoning
Less common nowadays
Difficult to obtain poisons
Chemistry professors can
obtain poisons easily
207
Paul Agutter
208
Paul Agutter
Convicted of poisoning
his wife with atropine
Atropine from
his research lab
Paul Agutter
209
Paul Agutter
How did he do it?
Added atropine to
his wifes gin & tonic
Paul Agutter
Tried to mislead investigators
Added atropine to the tonic
water at local supermarket
211
Paul Agutter
Found out by the police
Lesser atropine added to tonic
bottles than to his wifes drink
Wife survived
Convicted of attempted murder
212
Georgi Markov
213
Georgi Markov
Bulgarian Dissident
Defected to Britain in 1971
Worked for BBC
World Service
Georgi Markov
214
215
Autopsy results
Puncture wound
Tissue sent to Porton Down
Found a tiny metallic sphere
216
SEM-EDX results
90% platinum, 10% iridium
Sphere was hollow
Enough space for
2 mg of poison
SEM-EDX of sphere
217
Poison used
Complex polypeptide
Ricin
Umbrella
Pellet gun
Umbrella
Markov: injected pellet close to blood vessel
Ricin absorbed rapidly
Question
Was Georgi Markov murdered by
the Bulgarian Secret Service?
Likely
221
Alexander
Litvinenko
222
Alexander Litvinenko
KGB then FSB officer
1998
2000
Asylum in London
2006
Alexander Litvinenko
Hair loss
Thallium poisoning?
No thallium detected
Poisoned with Polonium-210
Alexander Litvinenko
after being poisoned
224
Polonium
Radioactive
Occurs in trace amounts
Manufactured in nuclear reactors
Russia
225
Polonium
Contained 210Po is not very dangerous
If ingested
No barrier between radioactive
atoms and biochemical molecules
Radiation poison
226
Radiation
Energy given out is
highly characteristic
210Po
found at over 30
locations in London
Tracked to two British
Airways planes
227
Summary
1
Summary
5
Xenobiotics
Alcohol
Paracelsus