Download Chapter 13-Toxicology

Forensic Toxicology
What are toxins?
Forensic Toxicology
• Study of drugs and poisons and their adverse
affects on the human system
– Pharmacokinetics (what drug does to person?)
– Pharmacodynamics (what body does to the drug?)
>75% of forensic science investigations involve drug use!
Drug/Toxin Vocabulary
• Dose
– Amount of drug that enters the body
How is a dosage determined?
LD (Lethal Dose)50
Lethal Dose-50
LD50 Calculations:
Cyanide (for 150 lb human - ~ 70 Kg)
(70Kg)(10mg/Kg) = 700 mg (0.70g)
Nicotine (e.g.; from Cigarettes)
(70Kg)(2 mg/Kg) = 140 mg (0.14g)
(note 1 cig. = ~ 2 mg Nicotine)
Ethanol
Substance
LD50 (mg)
Aspirin
Ethanol
Morphine
Caffeine
Heroin
Lead
Cocaine
Cyanide
Nicotine
Strychnine
Batrachotoxin
1750
1000
500
200
150
20
17.5
10
2
0.8
0.002
(70Kg)(1000mg/Kg) = 70,000mg (70g)
2, ½ oz shots of vodka= ~28g EtOH
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Lethal Nature and MSDS Sheets
• Materials Safety Data Sheets - provide specific
toxicological, chemical and physical data about a
compound.
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Physical Properties and Names
Chemical Reactivities
Incompatibilities
Safe Handling
Toxicology (symptoms and means of exposure)
Safety and First Aid
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MSDS Sheets - Example
NICOTINE
(S)-3-(1-Methylpyrrolidin-2-yl)pyridine CAS # 54-11-5
3-(1-Methyl-2-pyrrolidinyl)pyridine RTECS # QS5250000
b-Pyridyl-a-N-methylpyrrolidine
ICSC # 0519
1-Methyl-2-(3-pyridyl)pyrrolidine
EC # 614-001-00-4
C10H14N2
Molecular mass: 162.2
TYPES OF
HAZARD
ACUTE HAZARDS/
SYMPTOMS
FIRE
Combustible. Gives off irritating
NO open flames.
or toxic fumes (or gases) in a fire.
EXPLOSION
EXPOSURE
INHALATION
SKIN
PREVENTION
FIRST AID/
FIRE FIGHTING
Powder, alcohol-resistant
foam, water spray, carbon
dioxide.
Above 95°C explosive vapor/air
Above 95°C use a closed
mixtures may be formed.
system, ventilation.
PREVENT GENERATION OF MISTS! AVOID EXPOSURE OF (PREGNANT) WOMEN!
IN ALL CASES CONSULT A DOCTOR!
Burning sensation. Nausea. Vomiting.
Convulsions. Abdominal pain. Diarrhoea. Headache.
Sweating. Weakness. Dizziness. Confusion.
Ventilation, local exhaust, or breathing protection.
Fresh air, rest. Refer for medical attention.
MAY BE ABSORBED! Redness. Burning sensation
Protective gloves. Protective clothing. Remove contaminated clothes.
Rinse and then wash skin with water and soap. Refer for medical attention.
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Toxicity and Exposure Time
• Acute Toxicity
– Adverse effects within short time of toxin exposure
• Chronic Toxicity
– Condition caused by prolonged exposure to a toxin
Poisons (and drugs)
• Corrosive Poisons - Substances that actually
destroy tissue outright
• Metabolic Poisons - Affect biochemical
mechanisms
Corrosive Poisons
• Substances that actually destroy tissue outright
– Acids/Bases (Alkali)
• Sulfuric Acid (H2SO4)
• Hydrochloric Acid (HCl)
• Sodium Hydroxide (NaOH; cleaners)
– Death can result from a little as 1 oz. H2SO4
• Works by dehydrating tissues
• Cells die fast because water is removed AND proteins are
destroyed by acid-catalyzed hydrolysis of peptide bonds.
Corrosive Poisons
• Warning Signs:
– Corrosive toxins interact with body sensory systems
to alert of exposure:
• Ammonia (above 0.01% in air) causes choking
• Acids interact with nerves to send pain signals upon
exposure
– Some lack clues!
• Hydrofluoric acid (very corrosive; used in electronics) destroys both tissue / bone but does not cause pain upon
tissue exposure . Only sends pain when BONE is
exposed.
• Bases (NaOH) slippery
Corrosive Poisons
• Some are toxic because of reactions
– Phosgene (mustard gas, and in plastics industry) - if
inhaled it reacts with water in lungs to form HCl.
• Causes Pulmonary edema (fluid in lungs) because it
draws water from surrounding tissues - victim drowns.
• Phosgene does not have good warning properties (smells
like new-mown hay and lung reactions are slow.
O
+ H2O(l)
C
Cl
Cl
2HCl(aq) + CO
2(g)
Metabolic Poisons
• Affect Biochemical Mechanisms:
– Carbon Monoxide (Gas) - colorless, odorless, toxic suicide or homocide.
• Binds to iron in hemoglobin and only very slowly is released displacing oxygen - Carboxyhemoglobin is 140 time more
stable than oxyhemoglobin
• Breathing 0.1% CO in air for 4 hours converts 60% of
hemoglobin to carboxyhemoglobin!
• Not a cumulative poison (given time, the free hemoglobin is
released)
Hemoglobin Transport
Fe site - point
of attachment
(Heme groups in orange)
O
O
O
H2O
HEME
HEME
C
CO
HEME
O2
Red
Oxyhemoglobin
Blue
Red
Carboxyhemoglobin
Metabolic Poisons
– Cyanide (suicide or homicide - Tylenol murders)
• Common industrial agent (plastics formation, electroplating,
metal-ore processing)
• NaCN reacts with acids to form HCN (gas) - weak odor of
almonds
• Naturally occurs in seeds (protects seeds until they germinate).
• Very fast working (seconds)
• Causes asphyxiation
– binds tightly with iron so that, even though lots of oxygen gets to cells,
they can’t use it to support life.
• Eventually, cyanide is removed by enzyme.
• Administer large amounts of thiocyanate can be effective ANTIDOTE.
Cyanide Poisoning
Cyanide is commonly thought of as a gas, but you also can be poisoned
by it if you ingest wild cherry syrup, prussic acid, bitter almond oil, or
large amounts of apricot pits. Cherry seeds, peach and plum pits,
corn, chickpeas, cashews, and some other fruits and vegetables
contain cyanogenic (i.e., cyanide-forming) glycosides that release
hydrogen cyanide when chewed or digested. However, cyanide
poisoning from a food source is rare.
Arsenic Poisoning
• As commonly occurs in pesticides, shrimp,
pressure treated wood (Paris green), old
wallpaper (green color)
• React with SH groups of enzymes - stopping
their normal function
• Accumulates in the body (not eliminated)
• Used as a poison gas in WWI - led to search for
antidote
Mercury Poisoning
• In Fluorescent lamps, dental amalgams, fungicides
• Neuron toxin-many problems including:
– Impaired vision, hearing, and speech
– Brain damage
• Interferes with enzymatic actions (seleno-enzymes
which normally prevent oxidation damage)
Mad Hatter’s Disease
• History
Lead Poisoning
• Romans – Lead cooking vessels, cosmetics, Lead Plumbing (downfall
of Rome - Pb in Emperor’s wine and water lead to mental illness)
– See high Lead levels in bone evidence
– “plumbing” from Latin word for Lead plumbum
• Modern - Leaded Gas, Paint, water pipe joints
– Plumbing - (joints) EPA allows max 15 ppb, many cities have 500
ppb.
– Paint - PbO (white paint) - children ingest (now use TiO2 - nottoxic)
• Pb displaces physiological metals in chemical reactions
Types of Abused Drugs
• Narcotics - relief from pain and bring sleep.
– Narcotics are analgesic - relieve pain by depressing nervous
system (opium, morphine, heroin, codeine, opiates - oxycontin,
methadone).
• Hallucinogens - alter normal thoughts, perceptions and
moods (PCP, LSD, mescaline, MDMA, ecstasy).
• Depressants - depress functions of central nervous
system, cause calm and bring about sleep (alcohol,
barbituates). Tranquilizers are depressants.
• Stimulants - increase alertness and activity (cocaine,
amphetamines).
• Steroids - promote muscle growth (androgen,
testosterone, anabolic steroids).
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Narcotics
• Oxycontin:
– For Chronic Pain
– One of most abused
drugs in U.S
– Names: Oxy, O.C., killer
and hillbilly heroin
– Highly addictive with
physical dependence
Narcotics
Narcotics
Unripe pod of Poppy Plant
Opium is a gummy, milky juice
Morphine
Codeine
Heroin (synthetic)
Pain Relief
“High”-Happiness
(3-4hrs)
Drowsiness
Bitter Taste
IV Use
35% Pure!
Additives:
Street Names: H, Horse, Scag, Smack, Stuff
Field test uses reagent called marquis for a purple color
Quinine, starch,
lactose, Novocain
Heroin Symptoms
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Euphoria
Drowsiness
Contracted pupils
Needle marks
Blood stains
Other Opiates
• Methadone
– Related to heroine
– Eliminates the “high” if taking heroine
– Helps break heroine habit
Hallucinogens
• Hallucinogens - alter normal thoughts,
perceptions and moods (PCP, LSD, mescaline,
MDMA, ecstasy).
• Marijuana most common (derived from
Cannabis or “hemp” plant).
– Derive resin from plant secretions that is extracted
with organic solvents.
– In use for 1000’s of years.
– Brought to the US ca. 1920.
Marijuana
Pot, Grass, Wacky Baccy, Hash, Ganja,, Hash Oil, weed, Tree, greens,
Wild weed 5-15 ft
Odd leaf number, serrated edge
Crush leaves with flower, stem and
seed
Plant Resin=Hashish
THC Active Ingrdient
Can tentatively be identified by the DuquenoisLevine color test
Marijuana
Symptoms
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Lack of coordination-Danger to Drive!
Reduced Reaction Time-Danger to Drive!
Red eye
Dilated pupils
Increased heart rate
Irrelevant giggling
Spice-Synthetic Marijuana
• a.k.a: “K2, Fake weed, Yucatan Fire, Skunk,
Moon Rocks”
• 5 active chemicals-cannabinoids
• Illegal, Controlled Drugs, Schedule 1 DEA
• Big use by high school age
• Symptoms: rapid heart rate, vomiting, agitation,
confusion, and hallucinations-psychotic reactions
• Regular users may experience withdrawal and
addiction symptoms.
Spice Problem
• Negative Traditional Drug Test Results
• But…Can detect metabolites of JWH-018 in
urine
LSD- Street Names:
Acid, Boomers, Yellow Sunshines, Cid, Doses, and Trips
•Derived from Ergot Fungus (on
grasses/grains)
•First described in 1943 after “accidental”
lab ingestion (potent - 25mg for long
lasting effects!)
•25 microgram causes hallucinations for
12hrs
•Mood swings
•Anxiety
•tension
lysergic acid
diethylamide
Purple-Blue Van Urk
Presumptive Test
Other Hallucinogens
• Phencyclidine (PCP)- (phencyclidine)
Originally an IV anesthetic but hallucinations
created a problem
Street Names: Angel Dust, Crystal, Hog,
Supergrass, Killer Joints, Ozone, Wack,
Embalming Fluid, and Rocket Fuel.
• Mescaline- ancient American Indian drug
derived from a cactus
• Psilocybin- Street Name: Shrooms,
Mushies, and Mexican Magic Mushrooms
• STP- synthetic from the 1960s
Other Hallucinogens
• MDMA (Ecstasy, E, Adam, XTC, Fantasy, Date-Rape Drug)
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Get Abundant Energy
Increased Color perception
Dehydration-Drink a lot
Enhanced empathy
Brain cell damage
Anxiety
Panic
Insomnia
Hallucinations
Psychosis
Memory loss
Hypertension
Depressants
• Depressants - depress functions of central
nervous system, cause calm and bring about
sleep (alcohol, barbituates). Tranquilizers are
depressants.
– Downers - relax, create feeling of well-being,
produce sleep.
– Act on central nervous system.
– Usually taken orally.
– Also includes tranquilizers (e.g., librium and Valium)
and “glue sniffing” (toluene, gasoline, freon, etc.) - all
effect central nervous system. Major problems chemical eposures cause permanent liver, kidney,
heart and brain damage.
An advanced lesson on alcohol!
Alcohol
• No. 1 abused drug with more related deaths per
year than any other.
Alcohol Specifics (Route)
• Alcohol in stomach (20% absorbed) and
intestine
• Absorbed within minutes into bloodstream
– Timing affected by:
– Time taken to consume drink
– Alcohol content
– Amount consumed
– Stomach contents
Alcohol Specifics (Route)
• Alcohol distributed to watery parts of body via blood
• Liver, 1st stop- Begin detoxification (0.015% w/v per
hour
• Heart
• Lungs-Alcohol vapors out with breath
– Using Henry’s Law can relate amount of alcohol in breath
to amount in blood
• Brain-impair neuron transmission
Breath Test Instruments
• Breathalyzer
– Blow 52.5ml of alveolar air into machine
– Added to potassium dichromate, silver nitrate,
sulfuric acid and water
– Alcohol converts dichromate to acetic acid
– Dichromate amount reduced-measured via a
spectrophotometer in machine (must be
calibrated! and chemicals pure)
Ethanol
• Depressant, not a
stimulant.
• Continued use may
lead to physical
dependency.
• Even low doses can
cause impairment
(with the feeling of no
effect).
Alcohol
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Sedative
Vasodilator=Blood increased to extremities
Diuretic
Respiratory Depression
Gastric irritation
Slur Speech
Acute Toxicity=coma and death
Chronic Toxicity=liver damage
Other Depressants
• Barbiturates (“Downers, Yellow Jackets, Blue
Devils, Reds, Barbs”)
– Downers- Suppress Central Nervous System
– Derived from Barbituric Acid
– Sedatives taken orally
– Physically Addictive
– Ex. Amobarbital, Secobarbital, Phenobarbital etc.
Presumptive Test
• DILLE-KOPPANYI
• Used to test for barbiturates
• Turns violet-blue
Other Depressants
• Methaqualone (Quaaludes)
– Sedative
– Muscle relaxant
• Tranquilizers
– Relaxed but not impaired or sleepy
– Ex. Miltown, Librium, Thorazine and Valium
– Physically and mentally addictive
Ketamine =Horse
Tranquilizer
(Special K, Kit Kat)
Symptoms of Tranquilizer Abuse
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Slurred speech
Staggered Gait
Poor coordination
Poor judgment
Appears drunk but no alcohol smell
Other Depressants
• Glue Sniffing, Sniff aerosol propellants and
solvents
– Suppress Central Nervous System
– Euphoria
– Slurred speech
– Impaired judgment
– Double vision
– Risk liver, heart, brain damage and death
Glue Sniffer Meeting
Club Drugs/Date Rape Drugs
Date Rape Drugs
Flunitrazepam
(Rohypnol)
Ketamine
MDMA (Ecstacy)
GHB
Date Rape Drugs
Rohypnol, Ketamine, GHB, Ecstasy
• GHB (depressant) effects can be felt within 15 minutes after ingestion.
Mixed with alcohol GHB can cause the central nervous system to shut
down, lead to loss of consciousness, and possibly result in a coma or
death.
• Rohypnol (depressant) effects begin within 30 minutes, peak within 2
hours, and may persist for up to 8 hours or more, depending upon the
dosage (Street Names: Roofies, Rophies, Roche, Forget-me Pill,
Circles, Mexican Valium, Rib, Roach-2, Roopies, Rope, Ropies,
Ruffies, and Roaches)
• Ketamine (hallucinogen) causes the person to feel as if their mind is
“separated” from the body. The drug causes a combination of amnesia
and hallucinations. Also, it stops the feeling of pain and lowers the heart
rate leading to oxygen starvation to the brain and muscles. Vet Medicine.
• Ecstasy (hallucinogen)causes psychological difficulties, including
confusion, depression, sleep problems, drug craving, severe anxiety, and
paranoia-during and sometimes weeks after taking Ecstasy.
Date Rape Drugs:
What You Can Do to Protect Yourself?
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Don't accept drinks that you did not open yourself.
Don't exchange or share drinks with anyone.
Don't drink anything out of a punch bowl.
Monitor the behavior of friends who seem more intoxicated
than the amount of alcohol would warrant.
Never consume a drink that you have not mixed yourself,
or have not watched someone else prepare.
Never accept a drink from someone you don't know and
trust.
At parties or clubs with friends never leave your drink unattended.
Be aware of your surroundings - Listen for the street names of the
drugs - Trust you instincts
Date Rape Drug Offenders
Stimulants
• Stimulants - increase alertness and activity
(cocaine, amphetamines).
– Amphetamines - synthetic drugs that stimulate the
central nervous system.
– Once stimulant wears off then severe depression
usually sets in - requiring more stimulant (speed
binge).
– Dilated pupils, insomnia, panic, confusion, increased
heart rate, hypertension
•
Stimulants
Amphetamines (uppers or speed):
– Synthetic
– Alert, happy, hyperactive then fatigued (excessive sleep) and
depressed
– Loss of appetite
– IV use
– Psychologically addictive
Amphetamines
Methamphetamines
($450-$2,000/oz)
“Ice”
Bath Salts
• One or more synthetic chemicals related to
cathinone, an amphetamine-like stimulant
• Effects: euphoria and increased sociability
and sex drive, but some users experience
paranoia, agitation, and hallucinatory
delirium; some even display psychotic and
violent behavior, and deaths have been
reported in several instances.
• As soon as an ingredient is made illegal,
chemists alter chemical’s structure.
Other Stimulants
• “Ice”
– High,
– Stay up for days then depressed, tired and hungry
– Smoked
– VERY POTENT
– Violent, destructive, paranoid schizophrenic-like
($3,600-$7,000/oz)
Before ICE
After ICE
Stimulants
• Cocaine – Interferes with dopamine, a chemical messenger associated with
pleasure; continuous stimulation of “receiving” neurons, leads to
euphoria
– The powdered, hydrochloride salt form of cocaine can be snorted or
dissolved in water and injected.
– Crack=This form of cocaine comes in a rock crystal that can be
heated and its vapors smoked. The term “crack” refers to the
crackling sound heard when it is heated.
– acute cardiovascular or cerebrovascular emergencies, such as a
heart attack or stroke.
– constricted blood vessels, dilated pupils, and increased temperature,
heart rate, nasal problems, head ache, fatigue and high blood
pressure.
Ground to powder
and chemicals
added
Coca Plant
10 pounds of leaves= 1 ounce of cocaine
Crack
Cocaine Paraphenalia
• http://channel.nationalgeographic.com/channel/d
rugs-inc/videos/cocaine/
Steroids
• Anabolic Steroids
(Roids)
Steroids
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Synthetic (Like Testosterone)
Enhanced Muscle Growth
Risk Liver Damage
Reduced sex drive (can cause impotence)
Reduce sperm production (can be permanent)
Severe Acne
Premature baldness
Masculinizing in females and infertility (i.e. pronounced jaw)
Feminine characteristics in men (grow breasts)
Teenage suspension of bone growth
Mood swings and aggressive behavior (increases with cycling)
Workload of Forensic Toxicologists
Dead Person:
• Murder by a poison or accidental exposure?
• Overdose?
• MVA-drug related?
Workload of Forensic Toxicologists
• Living Person:
– Drink/drug driving
– Drug Facilitated Sexual Assault (DFSA)
– Professional/amateur athlete
– Workplace drug testing
Even more work for toxicologists..
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Air (ex. Asbestos, carbon monoxide)
Water (ex. coal and fracking industry slurries)
Soil (ex. radiation from nuclear meltdowns)
Foods (ex. food poisoning)
Cosmetics
Where to look in body for a toxin?
Specimen Collection
Each has it’s own set of problems and advantages
Fluids:
Organs:
Blood
Skin
Urine
Lungs
Vitreous Humor
Hair and Fingernails
Oral Fluid
Liver
Semen
Kidney
Stomach Contents
Bone
Bile
Other (heart, brain, etc.)
Vitreous Humor - clear, gel-like mass that fills the space between the lens and the retina.
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Additional Sources
Vomit
Earwax
Semen
Feces
Sweat
Meconium (fetal poop)
Amniotic Fluid
Umbilical Cord Blood
Milk
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Issues with sampling..
• Blood Samples:
1. If taken near a solid organ after death may
get very high (and inaccurate) drug
concentrations
2. Toxins will diffuse out of organs after
death
3. Blood should therefore be taken from
femoral artery which is far from organs
Issues with sampling..
• Liver - concentrates and stores drugs for long times.
– good for detection but problematic for concentrations
• Urine - tends to be concentrated form of compounds.
– Can’t be sure of body concentration since it is unknown how
long it has been accumulating in the body.
Sampling
• Bile - Useful for detection but not concentration.
• Kidney - Similar to Bile.
• Vitreous Humor - Correlates well with femoral blood
for most compounds.
• Hair and Fingernails - Good for some compounds
with timelines possible.
• Oral Fluids - Can be easily disguised. Procedure
still in development
.
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Drug Metabolism Issues
Analyte vs. Metabolite
• Analyte= Compound analyzing for
• Metabolite=body can change chemical nature of
drug (Heroin converted to Morphine)
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Drug ID
Immunoassay
TLC
GC
HPLC
GC/MS*****
LC/MS
(AA; ICP-MS)
Separation, detection, identification and measurement of drugs in biological specimens