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Forensic Toxicology
Toxicology
Study harmful effects of toxins on animals
and plants
Many different types:
• Environmental (air, water, soil)
• “Consumer” (foods, pharmaceuticals,
cosmetics)
• Medical, clinical, forensic
Clinical vs. Forensic Toxicology
• Clinical:
–emergency screening (e.g.
overdose)
–therapeutic drug monitoring (TDM)
(limited menu of drugs)
Testing only done if likely to affect the management and
course of clinical treatment.
Forensic Toxicology
Broad based screening and measurement for legal
purpose
– Postmortem (ME/Coroner)
– Criminal (MVA; assault)
– Workplace drug testing
– Sports (human & animal)
What Do Forensic Toxicologists Do?
• Analyze blood and other human fluids or
tissues for alcohol, drugs and poisons
(analytical toxicology)
• Interpret analytical results
• Considerable experience required
Analytical Toxicology: What do you need?
• Strong Chemistry background
– Analytical, organic, physical
• Accuracy and attention to
detail
• Computer skills
• Troubleshooting skills
• Willingness to do repetitive
work
• A “strong stomach”
• Common sense, patience
Why?
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Cause of death?
Contribution to death?
Cause Impairment?
Explain Behavior?
• Footnote: Drug or alcohol caused deaths
almost never show specific signs at autopsy.
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How?
Immunoassay
TLC
GC
HPLC
GC/MS
LC/MS
(AA; ICP-MS)
Analytical Basis of Toxicology
Separation, detection, identification and measurement of drugs in biological specimens
• Immunoassay – 10%
• Chromatography – 85%
• Other – 5%
The Analytical Process
• Sample receipt
– Chain-of-custody
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Review request and information
Decide on testing to be performed
Analytical testing
Review, evaluate and interpret results
What are the (Analytical) Problems?
• 1.
Endogenous substances
• cholesterol, fats, proteins
• putrefactive amines
• 2.
Enormous range of drug concentrations
• therapeutic concentrations range over at least 100,000 fold
• can vary >1000x even for single class of drugs
• 3.
Some drugs cannot be readily detected
• Analytical conditions may not be appropriate
• Drug/poison may be new or very unusual
“Forensic” Alcohol
vs.
Forensic
Clinical
Intoxication?
• A young man appeared intoxicated on a transCanada Greyhound bus
• Police met the bus; escorted the man to hospital at
2.30 am
• Examined; released to police & placed in cells to
“sober-up”
• Found with agonal breathing 7 am; died shortly
after
• Blood alcohol “0”; acetone 170 mg/100mL
• Blood glucose 1930; vitreous 1224 mg/100mL
Postmortem Fermentation
Blood ON ITS OWN is UNRELIABLE as a
specimen for assessing the presence of
alcohol at the time of death.
Blood
Vitreous
Postmortem Fermentation
• 86 y.o. lady died suddenly from heart disease;
autopsy ordered and blood taken for routine
toxicology
• Blood alcohol 320 mg/100 ml
– Urine 0; bile 20 mg/100 ml
• No evidence of alcohol abuse
• No alcohol in morgue
• Meds in blood and urine correlated
– Warfarin & digoxin; also blood typing
Methanol Cases…
Methanol causes: blindness, acidosis, hypoxic brain damage and death
Methanol Intoxication?
 Severe MVA
 Ethanol not detected,
but…
 Urine MeOH 530 mg%
 Liver 190, 300 mg%
 Spleen 20, 70 mg%
 Explanation?
Carbon Monoxide Deaths
Some are obvious…
Carbon monoxide binds to hemoglobin 200x stronger than oxygen!
Carbon Monoxide Deaths
Some sources are less obvious…
Postmortem Redistribution
 False Premise
• Blood levels of drugs after
autopsy reflect those at the
time of death
 Reality
• Many drug levels increase
after death; some 2–10 fold
• Many mechanisms
• Some drug levels decrease
after death (e.g. cocaine)
Other Interpretation Issues
• Combined Drug Deaths
– additive or synergistic toxicity
• Tolerance
– need to increase dose for same effect
• Genetically Impaired Metabolism
– 7-10% Caucasians are slow
metabolizers
• Drug-Drug Interactions
– can cause synergistic or fatal toxicity
Other Interpretation Issues
• Drug Accumulation
– caused by decreased metabolism or
clearance
• Medical Artifacts
– intravenous lines; incomplete
distribution
• Delayed deaths
– drug toxicity causes physiological
damage; drugs levels may fall to near
zero before death occurs
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)
Breathalyzer
Alcohol and NYS Law
• 0 Tolerance Law
– Less than 21
– Drive after drinking
– Blood alcohol .02-.07 violation of DWAI
– Suspend license
– Fine
– Increased insurance rate
– jail
Alcohol and NYS Law
• Everyone else:
– DWAI at .08 blood alcohol level
– 1st Offence=15 days jail, $300-500 fine, 90 day
license and registration suspension, surcharge,
victim panel
– 2nd Offence=30 days, $500-750 fine, 6 month
license and registration suspension, surcharge,
victim panel
– Future=Felony
What’s your blood alcohol level?
• http://www.ou.edu/oupd/bac.htm