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1 Learning Objectives List the different types of poisons and their effects Explain factors affecting LD 50 results Illustrate why route of administration is important Explain how toxicity is measured using LD 50 1 3 4 Describe the modes of actions of different types of poisons 2 5

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  • 1Learning Objectives

    List the different types of poisons and their effects

    Explain factors affecting LD50 results

    Illustrate why route of administration is important

    Explain how toxicity is measured using LD50

    1

    3

    4

    Describe the modes of actions

    of different types of poisons2

    5

  • 2Toxicology

    Environmental

    Science of poisons and poisoning

    Reasons Accidental

    Occupational

    Deliberate

  • 3Toxicology

    Less common now

    Chemicals tightly controlled

    Use of poisoning to commit murder

    Common in the old days

  • 4Corrosives

    Strong acids and alkalis

    Concentrated

    sulfuric acid

    VitriolGHS symbol for corrosives

  • 5Victim of acid attack

    in Cambodia, 2007

  • 6Victims of acid attack

    in Bangladesh, 2011

  • 7Acid attack case in

    Malaysia, 2009

  • 8Before and after

    her acid attack

    Ameneh Bahrami

    Ameneh Bahrami

    Drastic effects of sulfuric

    acid on the human body

  • 9Irritants

    Other effects after absorption

    Lead, mercury, arsenic

    Cause nausea or diarrhoea

    Irritate the gut

  • 10

    Systemic Poisons

    Interfere with action

    of mitochondria

    Hemoglobin

    Attack biochemical systems in body

    Cyanide

    Carbon monoxide

    1

    2

  • 11

    Systemic Poisons

    Affects the nervous systemStrychnine3

    Morphine4

    Atropine Affects the nervous system5

    Synthetic pesticides and nerve agents6

  • 12

    Systemic Poisons

    Inorganic poisons7 Arsenic

    Antimony

    Mercury

    Thallium

  • 13

    Cassava plant

    Cassava root is

    a staple food

    Cyanide

  • 14

    Cutting open the cassava root

    Cyanide

    Few cases yearly

    Plant releases cyanide

    Cassava root not properly prepared

  • 15

    Carbon Monoxide (CO)

    Deliberate

    Poisoning by CO

    Accidental

    Common

  • 16

    How CO works as a poison

    Blocks hemoglobin

    RBC containing hemoglobin

  • 17

    How CO works as a poison

    Protein

    Hemoglobin

    Responsible for oxygen transport

  • 18

    How CO works as a poison

    CO strongly bound; O2 cannot compete

    Always have some hemoglobin bound to CO

    Amount of CO in air too small to harm us

    CO always present in air

  • 19

    How CO works as a poison

    Blood is red because

    of the hemoglobin

    Poisonous when CO in air

    rises above a certain level

    A drop of blood

  • 20

    Gas-Hemoglobin Complexes

    Fe-O2 complex Red

    Fe-CO complex Pink

    Color of hemoglobin depends

    on the molecule bound to iron

  • 21

    Sources of CO

    Burning butane gas (C4H10)

    Partial combustion of fuel

    or other organic material

    In excess air

    In limited amounts of air

  • 22

    Sources of CO

    Burning butane (C4H10) in excess air

    Burning butane (C4H10) in limited amounts of air

    C4H10

    C4H10

    6.5 O2 4 CO2 5 H2O

    5.5 O2

    2 CO2 5 H2O 2 CO

  • 23

    Sources of CO

    Partial combustion of

    hydrocarbon fuels

    CO concentration can

    build up to toxic levels

    Improper ventilation

  • 24

    Presidente Hotel Poisoning

    5 people killed

    Rooms directly above parking garage

    Stairs leading up from garage to room

  • 25

    Carbon Dioxide (CO2)

    No oxygen

    Much less toxic than CO

    CO2 replaces airAsphyxiation

    Does not bind to hemoglobin

  • 26

    Lake Nyos, Cameroon, West Africa

  • 27

    Lake Nyos, Cameroon, West Africa

    Old volcanic crater filled up with rainwater

    CO2 seeped into lake

    Ground under lake giving off CO2

    Became a lake

  • 28

    Lake Nyos, Cameroon, West Africa

    Cold water in lakes lower layer

    CO2 unable to escape due to warmer

    water above the cold lower layer

    Super-saturated with CO2

  • 29

    Socrates

    (399 BC)

  • 30

    Socrates

    Convicted of corrupting

    the youths of Athens

    Encouraged

    them to think

    Socrates

  • 31

    Socrates

    Sentenced to death

    Poisoning

    Hemlock plant extract

    Hemlock plant

  • 32

    Socrates

    Hemlock contains

    various alkaloids

    Coniine

    Coniine

  • 33

    Socrates

    Symptoms experienced after drinking hemlock

    Numbness from feet upwards

    Paralysis reached heart and lungs

    Died

  • 34

    Augustus

  • 35

    Augustus

    Augustus

    Poisoned by Empress Livia

    Refused to eat food

    prepared for him

    Suspected that Livia

    wanted to poison him

  • 36

    Figs of Ficus carica

    Only ate fruits

    from his fig tree

    Livia injected

    poison into figs

    Caesar poisoned

    after eating fruits

    Augustus

  • 37

    Lakhvinder

    Cheema

  • 38

    2009

    Lakhvir SinghLakhvinder Cheema

  • 39

    Cheema and his fiance

    had leftover curry for dinner

    2009

  • 40

    Became very ill

    Called emergency services

    2009

    Food poisoning?

    Actual poisoning

  • 41

    Sent to the hospital

    Lakhvinder Cheema died soon after

    His fiance survived

    2009

    Lakhvir Singh convicted

  • 42

    Questions

    How had Lakhvir Singh done the poisoning?1

    How did she get such a potent poison?2

  • 43

    Aconitum ferox

    Native to the Himalayas

    Used as a poison in India

    Lakhvir Singh went to

    India to obtain plant

  • 44

    Aconitum ferox

    Went to Cheemas house

    Poisoned his curry

    Traces of plant found on her

    Convicted

  • 45

    Aconitum ferox

    Pseudaconitine

    Shuts down the

    nervous system

    Contains a very complex alkaloid

    Brain still working

  • 46

    William Congreve (1670 1729)

    Hell hath no fury likea woman scorned

  • 47

    Accidental poisoning

    Plants as a cause of poisoning

  • 48

    Blooming wild garlic

  • 49

    Accidental poisoning

    Wild garlic leaves vs meadow saffron leaves

    Wild garlic

    Look very similar

    Plants as a cause of poisoning

  • 50

    Accidental poisoning

    Meadow saffron

    Meadow saffron

    is highly toxic

  • Colchicine

    51

    Accidental poisoning

    Contains colchicine

    Anti-cancer

    Overdose

    leads to death

  • 52

    Accidental poisoning

    Wild garlic leaves vs meadow saffron leaves

    Potato tubers

    Potato plants

    Plants as a cause of poisoning

  • 53

    Accidental poisoning

    Potato fruits

    Potato tuber is harmless

    Potato fruits are toxic

  • 54

    Accidental poisoning

    Oxalic acid

    Potato fruits are toxic

    Contains oxalic acid

    Could have serious

    effects in children

  • 55

    Accidental poisoning

    Rhubarb

    Rhubarb

    Leaves are toxic

    Stems are edible

  • 56

    Toxins

    Natural substances produced

    by living species (animals)

    Attack biochemical systems

  • 57

    Box jellyfish

  • 58

    Black widow spider

  • 59

    Fugu fish

  • 60

    Fugu fish

    Fugu fish poisoning

    20 to 44 poisonings per year

    Japanese delicacy

    Tetrodotoxin poison

    Concentrated in

    internal organs

  • 61

    Fugu fish poisoning

    Chefs undergo training on how

    to remove toxic internal organs

    Poisonings because of amateur chefs

    7% fatality rate

  • 62

    Coastal Taipan

  • 63

    Cleopatra

    Egyptian Queen

    Cleopatra

  • 64

    Cleopatra

    Affair with Julius Caesar

    Julius Caesar

  • 65

    Cleopatra

    Mark Antony

    Got together

    with Mark Antony

    Lost the Final War of

    the Roman Republic

  • 66

    Cleopatra

    Wanted to commit suicide

    Tried out different means of suicide

    Wanted to look nice after death

    Snake poison

  • 67

    Asp

  • 68

    Biological poisons

    Responsible for botulism

    Clostridium botulinum

  • 69

    Botox

    Paralyze muscles

    Botox treatment

    Injection in a

    localized area

    Does not paralyze

    vital muscles

  • 70

    Biological poisons

    Responsible for anthrax

    Bacillus anthracis

    Weaponized anthrax

    available since WWII

  • 71

    Anthrax outbreak

    During the 9/11 crisis

    9/11 World Trade Centre attack

  • 72

    Anthrax outbreak

    Anthrax letters

  • Bruce Ivins

    73

    Anthrax outbreak

    Suspicion turned to Bruce Ivins

    U.S. Army microbiologist

    Had anthrax in his lab

    Committed suicide

  • 74

    Poisons

    Any substance which, if taken into or formedin the body, destroys life or impairs health.

  • 75

    Paracelsus

    Paracelsus

    First to think scientifically

    about poisoning

    Medicinal chemist

    Philippus Aureolus Theophrastus

    von Hohenheim (1493 1541)

  • 76

    Paracelsus

    All substances are poisons, there is none which isnot a poison. The right dose differentiates a

    poison from a remedy.

    Even water

  • 77

    Lethal water

    Water poisoning

    Over 7 litres Lethal dose

  • 78

    KDND, Sacramento, California

    Hold Your Wee For a Wii

    See how much water people can drink

    Winner wins Wii game station

  • 79

    KDND, Sacramento, California

    Drank about 7.5 L of water

    Went home, became

    unwell and died

    Jennifer StrangeFamily compensated

    U.S. $16 million

  • 80

    KDND, Sacramento, California

    Jennifer Strange placed second

    I didnt know what was wrong with me. Ijust knew I had never felt so sick in my life.- Winner of contest, Lucy Davidson

  • 81

    Fox glove

  • 82

    Fox glove

    Poisonous European wild plant

    Contains digitalin

    Potent heart muscle stimulant

    Over-consumption leads to death

  • 83

    Digitalin

    Also used clinically

    Failing heart

    Give controlled dose of digitalin

    Heart beats properly

  • 84

    Dose-Response

    Steepness of the curve

    Variable

    How to measure toxicity?

  • 85

    Measuring toxicity: LD50

    Lethal dose for 50 percent

    Amount of chemical required

    to kill half of the test population

  • 86

    Measuring toxicity: LD50

    How accurate is LD50?

    Lethal dose for 50 percent

    Amount of chemical required

    to kill half of the test population

  • 87

    Accuracy of LD50

    Vary according to administration of poison

    Oral administration vs direct injection

    1

  • 88

    Accuracy of LD50

    Assume similar LD50 values for humans

    Depend on species used for testing2

    Typically mice or rats

    Vary according to administration of poison1

  • 89

    Accuracy of LD50

    GuidelinesHow accurate is LD50?

    Lethal dose for 50 percent

    Amount of chemical required

    to kill half of the test population

  • 90

    Lethal doses

    Measure dose

    per unit bodyweight

    Types of poisonLethal dose

    (g / kg), mice

    Sodium cyanide 10 000

    Curare/

    strychnine500

    Tetrodotoxin 8 20

    Cobra neurotoxin 0.3

    Tetanus toxin 0.07

    Botulism toxin 0.03

  • 91

    Factors affecting LD50

    Size

    Age

    State of health

    1

    2

    3

    Larger doses for larger bodies (mg/kg)

    Metabolism changes with age

    Liver condition

  • 92

    Factors affecting LD50

    History4 Build up and loss of tolerance

    E.g. heroin addict

    Keep increasing dose

    Loses tolerance after a

    long time without heroin

    Tolerance

  • 93

    Factors affecting LD50

    Paradoxical reactions5 Rare but known

    E.g. anti-malarial medicine Lariam

    Side effects Depression

  • 94

    Factors affecting LD50

    Vanessa Brunt Went to South China

    Took Lariam

    Became very depressed

    Committed suicide

  • 95

    What Paracelsus did not say

    Poison must reach target organ

    Absorption into the body

    Build up to lethal levels before excretion2

    1

  • 96

    Mercury

    Swallow metallic mercury1

    Glass mercury

    thermometers

    Does not absorb

    into the body

  • 97

    Mercury

    Swallow metallic mercury

    Inject metallic mercury into bloodstream2

    1

    Ingest mercurous chloride (HgCl, calomel)3

    Ingest mercuric chloride (HgCl2)4

    More soluble in water, rapid absorption

  • 98

    Mercury

    Swallow metallic mercury

    Inject metallic mercury into bloodstream2

    1

    Ingest mercurous chloride (HgCl, calomel)3

    Ingest mercuric chloride (HgCl2)4

    Inhale mercury vapour5

  • 99

    Inhaling mercury vapour

    Absorbed very rapidly

    Go straight to bloodstream

  • 100

    King Charles II

    Many hobbies

    King Charles II

    Lab accident

    Interested in chemistry

    Poisoned by

    mercury vapor

  • 101

    Route of Administration

    Must reach target organ to be effective

  • 102

    Route of Administration

    Absorbed through digestive tract

    Oral administration1

  • 103

    Route of Administration

    Directly into bloodstream

    Fast and efficient

    Intravenous2

    Oral administration1

  • 104

    Route of Administration

    Rapidly from lungs to bloodInhalation3

    Fast and efficient

    Through mucus membranes4

    Intravenous2

    Oral administration1

  • In

    105

    Forensic Toxicology

    Food, drink, air

    Absorption &

    desorption of gases

    Detox

    Deposited

    in hair, nails

    Processing &

    absorption

    Out

    Feces, urine, sweat, exhaled air

  • 106

    Proteins are broken

    down into peptides

    Peptides broken down

    into amino acids

    Saccharides broken

    down into sugars

    What happens to your food?

  • 107

    Snake venom

    Complex peptides

    Drinking the venom?

    Relatively safe

    Milking snake venomPeptides converted

    to amino acids

  • 108

    Forensic Toxicology

    Enter bloodstream

    after digestion

    Liver = detox factory

    Get past liver to go to the rest of the body

  • 109

    Forensic Toxicology

    Enter bloodstream

    after digestion

    Liver = detox factory

    Get past liver to go to the rest of the body

  • 110

    Forensic Toxicology

    Blood flows past the

    lungs to rest of body

    Membrane around brain

    Prevent molecules from going into brain

  • 111

    Xenobiotics

    Strange molecules

    Pharmaceuticals

    Illegal drugs

    Natural substances

    Other substances

    Nicotine, caffeine

    Ethanol

  • 112

    Xenobiotics

    Accumulation in body Lead or strontium

    in bones

    Excretion Arsenic or thallium

    Transform

    Deposited in hair or fingernails

    Increase solubility

    1

    2

    3 Excrete

  • 113

    Xenobiotics

    Caffeine

  • 114

    Xenobiotics

    Goes into bloodstream

    Caffeine that is ingested

    Coffee berries

    Stimulates brain

  • 115

    Xenobiotics

    Liver wants to remove caffeine Transform it

    Caffeine

  • 116

    Alcohol

    Most common poison

    Controversial

    Essential?

    Or evil?

  • 117

    Alcohol

    Show evils of alcohol

    Gin

    Gin consumption

    was enormous

    Gin Lane

  • 118

    Alcohol

    Beer contains

    less alcohol

    Better than gin

    Beer Street

  • 119

    Distribution of alcohol

    What happens when someone drinks alcohol?

  • 120

    Distribution of alcohol

    Distributed via the cardio-vascular system

    Kind of drink

    Rate of adsorption depends on

    Stomach contents

  • 121

    Effect of alcohol

    Depress ability to make judgments

    Depress the Central Nervous System (CNS)

    Depress inhibitions

    Depress ability to react to situations

    Depress reflex times

  • 122

    How much is too much (legally)?

    Alcohol

    Blood alcohol concentration (BAC) after a drink?

    Calculated from the amount

    of alcohol consumed

    1

    2

  • 123

    How much is too much (legally)?

    Persons weight (kg)Amount of alcohol

    consumed (g)

    Widmark factorc = a / pr

    Men: r = 0.68

    Women: r = 0.55

    Max. conc. (g/ 1000 ml)

    Usually converted to

    mg / 100 ml of blood

  • 124

    If a man of 70 kg drinks a double whisky, what is the concentration of alcohol in his blood?

    Scenario

    Whisky = 43% alcohol A single = 25 cm3

    Density of ethanol = 0.79 gcm3

    Amount of alcohol consumed = 0.43 x 50 cm3 x 0.79 gcm3 = 17.0 g

    1

    3

    2

  • 125

    Scenario

    c = 36 mg per 100 ml of blood

    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

  • 126

    Effect of alcohol

    Effect of alcohol on the brain?

    Vary according to amount of alcohol

  • 127

    Effect of alcohol

    Blood alcohol

    conc. (mg/100 ml)Effects

    300Coma and anaesthesia, impaired circulation

    and respiration, possible death

    >450 Probable death due to respiratory paralysis

  • 128

    Elimination of alcohol

    Alcohol present in nature

    Biomechanism for eliminating alcohol from body

    Fermentation of food

  • 129

    Elimination of alcohol

    C5H5OH

    Ethanol

    CH3CHO

    Acetaldehyde

    CH3CO2H

    Acetic acid

    CO2Carbon dioxide

    Alcohol dehydrogenase

    (liver, small intestine)

    Aldehyde

    dehydrogenase

    (liver)

  • 130

    Elimination of alcohol

    95% - 98% of alcohol consumed end up as CO2

    2% - 5% excreted by kidneys and lungs

  • 131

    Distribution of alcohol

    Higher in arterial blood than in

    veinous blood during absorption

    Bones, fat, hair

    Uniformly throughout the body

    Except parts with low water content

  • 132

    Distribution of alcohol

    Post-mortem

    Same concentration as in the brain

    Usually measure blood alcohol

    Measure breath alcoholRoadside

    Gas chromatography

    Blood, urine, vitreous humor

  • 133

    Henrys Law

    How is breath alcohol related to blood alcohol?

  • 134

    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

  • 135

    Breath alcohol

    Measured at roadside using breathalyzers

    Chromium chemistry

    Breathalyzer

  • 136

    Breath alcohol

    Amount of K2Cr2O7 converted to Cr2(SO4)3

    2 Cr2(SO4)3

    K2Cr2O7 3 C2H5OH 8 H2SO4

    2 K2SO43 CH3COOH 11 H2O

    Measure loss of absorbance at 420 nm

  • 137

    Blood Alcohol Curve

    Blood alcohol levelat time of accident?

    Car accident

    One driver drives off

    Caught hours later

  • 138

    Blood Alcohol Curve

    Back calculate from timeof test to time of accident

    Plot BAC against time

  • 139

    Blood Alcohol Curve

  • 140

    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 70mg per 100 ml. Was the driver over the limit?

    Scenario

  • 141

    How fast peoples bodies eliminate alcohol

    Scenario

    Length of time between last drink and accident

    is enough to assume that alcohol absorption

    has ceased

    Down slope of blood alcohol curve

  • 142

    Lowest elimination rate

    Method 1

    Ct = C0 t

    = 12.5 mg ethanol per 100 ml blood per hour

  • 143

    Method 1

    Ct = C0 t

    t = time elapsed

    C0 = blood alcohol conc. at time of interest

    Ct = blood alcohol conc. at time of measurement

    = alcohol elimination rate

  • 144

    Method 1

    C0 = Ct + t

    C0 = 70 + 2(12.5) = 95 mg per 100 ml

    Lowest elimination rate

    Ct = C0 t

    = 12.5 mg ethanol per 100 ml blood per hour

  • 145

    Highest elimination rate

    Ct = C0 t

    = 25 mg ethanol per 100 ml blood per hour

    C0 = Ct + t

    C0 = 70 + 2(25) = 120 mg per 100 ml

    Conclusion: Man was above legal limit

    Method 1

  • 146

    Lowest elimination rate

    Method 2

    2 hours at 12.5 mg per hour = 25 mg

    12.5 mg ethanol per 100 ml blood per hour

    70 + 25 = 95 mg per 100 ml

    Add that 25 mg to the 5 am measurement

  • 147

    Highest elimination rate

    25 mg ethanol per 100 ml blood per hour

    Method 2

    2 hours at 25 mg per hour = 50 mg

    70 + 50 = 120 mg per 100 ml

    Add that 50 mg to the 5 am measurement

  • 148

    Both methods give same conclusion

    Man was above legal limit

    Methods 1 & 2

    Alcohol generates most work for toxicologists

  • 149

    Inorganic poisons

    Toxic elements

    Elements may neither be

    created nor destroyed

    vs organic poisons

    Robert Boyle

  • 150

    Inorganic poisons

    Detectable after burial

    Arsenic, antimony, mercury, thallium

    Detectable after death

    Detectable after cremation

  • 151

    Arsenic trioxide

    Once readily and

    legally available

    Arsenic trioxide

    Fowlers solution

  • 152

    Arsenic trioxide

    Flypaper

    Paper coated with glue

    Arsenic added to glue

    Flypaper

  • 153

    Arsenic trioxide

    Trisenox

    FDA (U.S.) approved for use in the

    treatment of some kinds of leukemia

  • 154

    Arsenic trioxide

    Inheritance powder

    Very common poison in the Victorian era

  • 155

    Arsenic poisoning

    confused with liver disease?

    A lot of money in 1869

    And adding arsenic?

    Due to arsenic?To test for arsenic

    Travelling court

    To drug him?

  • 156

    Widespread use of arsenic in poisoning

    Reliable method of testing for arsenic?

    Arsenic trioxide

  • 157

    Marsh Test

    Forensic use of

    testing for arsenic

    James Marsh

    Developed by James Marsh

    Now superseded by AAS

  • 158

    6 ZnAs2O3

    6 ZnCl22 AsH3 3 H2O

    12 HCl

    Marsh Test

  • 159

    Marsh apparatus

  • 160

    Can confirm presence of arsenic

    Can also estimate the amount of arsenic

    Marsh Test

    Only arsenic and antimony behave this way

    Chemists are able to tell them apart

  • 161

    Marsh Test very effective and credible in court

    Prosecution got better

    Defense

    Marsh Test

    Styrian Defence

  • 162

    The Styrian Defence

    Styrian peasants were

    eating arsenic trioxide

    Lethal dose

  • 163

    The Styrian Defence

    How did they do it?

    Slow release of As2O3?

    1

    Build up of tolerance?

  • 164

    The Styrian Defence

    Women

    Improve health?Why did they do it?2

    Men

    Blood vessels damaged

    Improve complexion?

    Improve sexual potency?

  • 165

    Florence

    Maybrick

  • 166

    Florence & James Maybrick

  • 167

    Liverpool, 1889

    Florence Maybrick

    Charged with murdering her husband with arsenic

    Tries the Styrian Defence

  • 168

    Liverpool, 1889

    Prosecution

    For use as a cosmetic face wash

    Arsenic purchased and soaked from flypapers

    Defense

  • 169

    Liverpool, 1889

    Prosecution

    Arsenic detected in James Maybricks body

    Defense

    Self-medication

  • 170

    Liverpool, 1889

    Verdict: guilty

    Sentenced to hang

    Commuted to 15 years in prison

    Died in 1941

  • 171

    Maine,

    New England

    2003

  • 172

    Maine, New England, 2003

    Arsenic poisoning case concerning achurch and the church congregation

  • 173

    Maine, New England, 2003

    27 April

    28 April

    Walter Morrill

    died in hospital

    Chemical tests run

    2 dozen people fell sick

    2 May

    Daniel Bondeson

    committed suicide

    Had sandwiches & coffee Arsenic in brewed coffee

    Arsenic in Morrills body & in surviving victims

  • 174

    Maine, New England, 2003

    Conclusion

    Daniel Bondeson added arsenic to the coffee during church service

  • 175

    Maine, New England, 2003

    From an old agricultural chemical

    Where was the arsenic from?

    Motive? Church dispute?

    Overdose?

  • 176

    Thallium

    Formerly widely available

    Rat poison

    Rat poison

  • 177

    Lethal dose 12 mg / kg

    Interferes with nervous system

    Due to chemical similarity with potassium

    Thallium

  • 178

    Characteristic symptom

    Hair will fall out

    Thallium

  • 179

    Graham Young

  • 180

    1962

    Sent to Broadmoor

    Psychiatric Hospital

    Detained and treatedGraham Young

    Murdered stepmother

    when he was age 14

  • 181

    1971

    Worked in a warehouse

    Poisoned the tea

    of his co-workersTea

    Released from hospital

  • 182

    Used low doses of thallium or antimony

    8 fell ill; 2 died

    Bob Egle Cremated

    Death triggered investigation

    Graham Young

    Fred Biggs

  • 183

    Bob Egle Cremated

    Thallium present in ashes

    Graham Young

    Thallium cannot be destroyed

    Graham Young convicted Life in prison

  • 184

    Shizuoka, Japan, 2006

    She did not hold a grudge against her mother she just wanted to do an experiment.

    Graham Youngs fans?

    17 year old girl poisoned mother with thallium

  • 185

    Arsenic and thallium

    Well known in toxicology

    Poisoning

    Other elements less well-known

    Analysis is rarely done

  • 186

    Barium poisoning

    Very uncommon

    Few people have access to barium compounds

  • 187

    Poisoned her father with barium acetate

    Father died

    Marie Robards

    No foul play suspectedMarie Robards

  • 188

    Went to University

    Scene where Hamlets father was murdered

    Marie Robards

    Affected by it Confessed to a friend

    Studied the play Hamlet

  • 189

    Victim exhumed

    Marie Robards convicted

    Investigation

    Presence of barium in his body

    Barium was stolen from school chemistry lab

  • 190

    Medical X-rays

    Soft tissues do not show up on X-rays

    Use of Barium

  • 191

    Barium meal

    Contains Barium

    X-ray after barium meal

    Show up digestive system on X-rays

  • 192

    Why doesnt it poison the patient?

    Barium sulphate is insoluble in water

    Barium meal

    Not absorbed by the body

    Excreted

  • 193

    Discovered inGermany in 1938

    Stockpiled by Hitler

    Never used in WWII

    Sarin

    CH3P(O)(F)OCH(CH3)2

  • 194

    Used by Iraqi military against Kurdish villagers

    Stops nervous system

    March 1988

    Aftermath of Halabja chemical attack

    Causes death

  • 195

    Released Sarin gas in Matsumoto in June 1994

    7 dead, 200 hospitalized

    Aum Shinrikyo Cult

    1995 Tokyo subway attack

    12 dead, 1000 hospitalized

  • 196

    How do nerve agents work?

    Interfere with biochemical mechanism

    Neurotransmission

  • 197

    Granule cell with axon

  • 198

    Mechanism of action of Sarin

    What if there is excess neurotransmitter?

    Continued nerve stimulation

    Twitching, convulsions, paralysis and death

    Often starts with blindness

  • 199

    Mechanism of action of Sarin

    When would there be excess neurotransmitters?

    Neurotransmitter concentration isregulated by acetyl cholinesterase

    Converts acetyl choline to inactive choline

  • 200

    Mechanism of action of Sarin

    Acetyl choline Choline

    Acetyl

    cholinesterase

    Inactive

  • 201

    Mechanism of action of Sarin

    Sarin is an acetyl cholinesterase inhibitor

    Excess acetyl choline cannot be destroyed

    Present in excess

  • 202

    Renegade soldiers stealschemical weapons

    Injected himselfwith antidote

    Hero exposed to nerve gas

    The Rock

    The Rock

  • 203

    Antidote to Sarin

    Opposite effect of Sarin

    Inhibits action of acetyl choline

    Atropine

    Atropine

  • 204

    Toxic if not taken as antidote

    Inhibits action of neurotransmitter

    LD50 (rat, oral) 500 mg / kg

    Atropine

  • 205

    Natural compound from Atropa belladonna

    Atropa belladonna

    Atropine

  • 206

    Atropine dilates the pupils

    Beautiful

    Used in optometry

    Atropine

    Atropa belladonna

  • 207

    Poisoning

    Less common nowadays

    Difficult to obtain poisons

    Chemistry professors can obtain poisons easily

  • 208

    Paul Agutter

  • 209

    Paul Agutter

    Convicted of poisoning his wife with atropine

    Atropine from his research lab

    Paul Agutter

  • 210

    Paul Agutter

    How did he do it?

    Added atropine tohis wifes gin & tonic

    Gin & Tonic

  • 211

    Paul Agutter

    Added atropine to the tonic water at local supermarket

    Tried to mislead investigators

  • 212

    Paul Agutter

    Found out by the police

    Wife survived

    Convicted of attempted murder

    Lesser atropine added to tonic bottles than to his wifes drink

  • 213

    Georgi Markov

  • 214

    Georgi Markov

    Bulgarian Dissident

    Defected to Britain in 1971

    Worked for BBC World Service

    Georgi Markov

  • 215

    Thursday, 7 Sept 1979

    Jabbed in the leg by anumbrella on Waterloo Bridge

    Died on Monday

    Admitted to hospital the next day

  • 216

    Autopsy results

    Puncture wound

    Found a tiny metallic sphere

    Tissue sent to Porton Down

  • 217

    SEM-EDX results

    90% platinum, 10% iridium

    Sphere was hollow

    SEM-EDX of sphere

    Enough space for 2 mg of poison

  • 218

    Poison used

    Complex polypeptide

    Isolated from castor oil plant

    Castor oil plant

    Ricin

  • 219

    Umbrella

    Pellet gun

    Also used on Vladmir Kostov (Paris, 1978)

  • 220

    Umbrella

    Markov: injected pellet close to blood vessel

    Kostov: injected pellet close to muscle tissue

    Ricin absorbed rapidly

    Slow absorbance of ricin

  • 221

    Question

    Was Georgi Markov murdered by the Bulgarian Secret Service?

    Likely

  • 222

    Alexander

    Litvinenko

  • 223

    Alexander Litvinenko

    KGB then FSB officer

    1998

    2000

    2006

    Serious critic of Russian government

    Asylum in London

    Became very ill and died in hospital

  • 224

    Alexander Litvinenko

    Hair loss

    Alexander Litvinenko

    after being poisoned

    No thallium detected

    Poisoned with Polonium-210

    Thallium poisoning?

  • 225

    Polonium

    Occurs in trace amounts

    Radioactive

    Manufactured in nuclear reactors

    Russia

  • 226

    Polonium

    Contained 210Po is not very dangerous

    If ingested

    Radiation poison

    No barrier between radioactiveatoms and biochemical molecules

  • 227

    Radiation

    Energy given out ishighly characteristic

    210Po found at over 30 locations in London

    Tracked to two British Airways planes

  • 228

    Summary

    Different types of poisons and their effects

    Measuring toxicity using LD50

    Importance of routes of administration

    1

    3

    4

    Modes of actions of different poisons2

  • 229

    Summary

    Alcohol

    Actions of arsenic, thallium, sarin, atropine

    6

    8

    Paracelsus7

    Xenobiotics5