1 Agree or Disagree?
• "All substances are poisons; there are none which is not a poison. The right dose differentiates a poison and a remedy.“ – Paracelsus Swiss-German Physician (1493-1541)
2 Central Focus Students can explain how forensic toxicologists use components of chemistry, biology, and medicine to interpret and justify their toxicology results from bodily tissues/fluids. Students can explain the proper techniques used to identify toxins in the body and describe why toxins have different effects on different people.
3 Learning Standards Ga. SFS3. Students will analyze the use of toxicology in forensic investigations. a. Classify toxins and their effects on the body. c. Evaluate forensic techniques used to isolate toxins in the body
4 Day 1 Essential Questions
• What is the difference between the type(s) of evidence that is analyzed by a forensic chemist versus a forensic toxicologist during a criminal investigation?
• Why is toxicology important to criminal investigations?
• How is lethality of a drug/poison determined?
5 Learning Targets. I can… • SFS1a – LK1: Match historical forensic scientists with their role in crime scene investigations • SFS3a – LK3: Describe how toxicology applies to criminal investigations. • SFS3a – LR6: Compare/contrast intoxicants, poisons, and toxins • SFS3a – LR7: Classify toxins and their effects on the body • SFS3a – LR8: Categorize toxin/poison exposure as intentional, deliberate, or accidental • SFS3a – LK4: Explain LD50 and how it applies to forensic toxicology
6 Toxicology • Mathieu Orfila – “Father of Toxicology” – “Traite des poisons” –first systematic approach to studying chemistry of poisons (arsenic)
• Study of poisons or the detection of foreign substances in the body that can have a toxic effect such as: – alcohol, industrial chemicals, poisonous gas, illegal drugs, drug overdoses
7 Importance of Toxicology Toxicology can: – Be a cause of death – Contribute to death – Cause impairment – Explain behavior
8 Toxicologist Examples
• Did a person die from a toxin or from natural causes? • Was the suspect’s behavior influenced by drugs in their system? • Was a suspect manufacturing illegal drugs?
60% of individuals arrested for most types of crimes test positive for illicit drugs at arrest.
9 Toxicologists • Toxicologists must understand chemistry, biology, and medicine. – Forensic toxicologists examine samples sent by forensic pathologist – BS or MS in related field; $35k-65k salary/year – Must be able to write up scientific report and serve as an expert witness – More experience necessary to be fully certified as a professional forensic toxicologist
10 Forensic Toxicology
• application of toxicology to the law, including – workplace or forensic drug testing – postmortem toxicology – human performance testing (alcohol and driving)
• Crime labs, medical examiners offices, hospital laboratories
11 Responsibilities of the Toxicologist
1. Know the chemical make-up, metabolites, and physiological actions 2. Understand drug metabolism 3. Understand chemical effects in healthy/unhealthy/addicted people. 4. Recognize signs/symptoms produced by the chemicals. Postmortem Forensic Toxicology
• Must start analysis ASAP after death – Suspected drug intoxication – Homicides – Arson fire deaths – Motor vehicle fatalities – Deaths due to natural causes
13 Is it always on purpose…?
People can be exposed to toxic substances: • intentionally— by treating illness or relieving pain • accidentally— by harmful combinations or overdoses • deliberately— by harming or killing others or by suicide
14 Lethal Dose 50 (LD50) • Measure of toxicity – mg of substance/kg body weight • Amount that kills 50% of the test population (usually rats/mice) within 4 hrs • Examples (in rats): – Sucrose 29,700 mg/kg (6 tsps/2.2 lbs) – Botulin toxin 0.000005 mg/kg -9 (1 x 10 tsp/2.2 lbs) 15 Factors Affecting Toxicity
• Chemical or physical form of the substance • How it enters the body • Body weight and health of person • Age and sex • Length of exposure • Other chemicals present
16 Classifying Toxic Agents • Length of Exposure – acute Toxicity: brief exposure – chronic Toxicity: exposure for months or years • Route of Exposure – direct contact – ingestion – inhalation – injection 17 Classifying Toxic Agents • Other classifications –Deteriorated tissue or function –Mechanism of action –Chemical structure • Heavy metals
18 Quick Check • Which of the following does NOT affect toxicity? A.Whether the agent is inhaled or ingested B.Whether the exposed organism is male or female C.Whether the agent is synthetic or naturally occurring D.Whether the exposure is continuous or sporadic E.Whether the exposed organism is a child or an adult
19 What is Poison? • any substance that, when taken in sufficient quantities, causes a harmful or deadly reaction • The key: Sufficient Quantities • Example: arsenic, water intoxication, blood doping
• What does “sufficient quantities” mean?
https://www.youtube.com/watch?v=lvHCfm qy4JM 20 Intoxicants, Poisons, and Toxins
• intoxicant: large amount needed to be lethal (ex. carbon monoxide or alcohol) • poison: a small amount is lethal (ex. cyanide) • toxin: poisonous substance from plant or animal; typically from microorganisms. Causes disease or death in small amounts. Note: Toxin can also be used generically to describe any chemical harmful to your body.
21 Day 2: Essential Questions
• What is a poison? How are they classified? • What are the steps for metabolism of a poison or drug? • What is the difference between a forensic chemist and a forensic toxicologist?
22 Learning Standards Ga. SFS3. Students will analyze the use of toxicology in forensic investigations. a. Classify toxins and their effects on the bodybody. c. Evaluate forensic techniques used to isolate toxins in the body
https://www.youtube.com/watch?v=GlpQK qf4LqI 23 Learning Targets. I can…
• SFS3c – LR9: Compare/contrast forensic toxicology and forensic chemistry • SFS3c – LR10: Predict the presence of a toxin based on metabolites identified using chromatography and/or spectrophotometry • SFS3 – LK5: Describe how drugs are metabolized by the body. • SFS3 – LS1: Design an experiment to explain how solubility of drugs affects how they interact with the body. 24 Is poisoning common? • Poisoning causes less than ½ of 1% of all homicides • Forensic toxicologists believe number may be higher; mistaken for natural causes • Accidental drug overdoses are more common https://www.youtube.com/watch?v=HH3_cUnvIQU *Note: this video is for educational purposes only…don’t be getting any ideas.
25 Common Poisons • Strychnine – (rat poison) severe muscle spasms and eventually muscles give out and can’t breathe • Cyanide – can be difficult to detect. Similar to the effects of suffocation. Causes cherry red blood. • Botulinum Toxin – Produced by bacteria. Paralyzes muscles and causes irreversible damage to nerve endings. Extremely deadly in very small amounts. – Most poisonous biological substance • Tetanus (also called Lockjaw)- produced by bacteria; causes violent muscle spasms
26 Common Poisons • Carbon Monoxide (CO) – one of the most common poisons – Binds to hemoglobin – Percent saturation: amount in the blood • 50-60% is typically fatal • In presence of alcohol or other drugs, 35- 45% may be fatal – Questionable fire? Low CO = likely dead beforehand; high CO = likely alive
27 Bioterrorism Agents Ricin- A poisonous protein in the castor bean. • Lethal in extremely small amounts • Can enter the body by inhalation, ingestion or injection • Causes death within a few hours Anthrax - Bacillus anthracis • Spreads to humans from infected animals • Enters the human body through: – Inhalation; causing breathing problems that usually result in death – Ingestion; becoming fatal in 25% to 60% of cases – Absorption via the skin; leading to death in about 20% of untreated cases
28 Metals as Poisons
• Metals – Arsenic – Iron – Mercury – Lead – Thallium – Antimony – Bismuth
29 Effects of Poisons
• Odor (arsenic: garlic; cyanide: almonds) • Hair loss (thallium) • Convulsions (strychnine) • Paralysis (botulism)
30 Effects of Poisons
• Skin color changes (carbon monoxide- cherry red; nitrates - blue) • Skin changes (arsenic: blisters) • Pupils (miosis, mydriasis)
31 Looking for toxins… • Challenging without supporting information – Nearby empty containers – Postmortem examination – Victim’s symptoms • Most toxins don’t change the body • Must look for other evidence in body fluids • Looking for small amounts; complicated by how body acts on the drug
32 Pharmacokinetics
• Pharma = poison/drug • Kinetics = movement • Study of bodily absorption, distribution, metabolism, and excretion of drugs • How our body processes chemicals and drugs
33 Ingestion
• How a drug/chemical enters the body • Can be with or without someone’s knowledge • Can depend on water solubility
• Quick check: What is solubility?
34 Absorption • How the drug/chemical gets into the blood stream – digestive tract, skin, lungs, eye, sites of injection – Most drugs/chemicals must get into the blood stream to travel to their target for an effect – Dependent on physical and chemical properties of the drugs
35 Distribution
• Drug/chemical getting to tissues throughout the body after absorption is complete – Circulates through blood – Dependent on solubility (fat vs. water) – Fat soluble will have higher volume of distribution and last longer
Which mouse would store toxins longer?
36 Metabolism • Biotransformation (also called metabolism) – Body breaks down the drugs/chemicals and changes them to get them out of the body • Body tries to make it more water soluble so it can be excreted • Metabolites – The new chemicals from the original toxin that occur as the body works to break down/get rid of a toxin
37 Metabolite Example: • Heroin is made from morphine • When someone ingests heroin, their body turns it into morphine
• What should a toxicologist look for?
38 Elimination
• Getting the drug out of the body • Zero Order: eliminated at the same speed until gone • First Order: elimination occurs at different speeds at different times • Urine, sweat, breath
39 Summary
• Ingestion absorption distribution metabolism elimination
• All work together to get drug/chemical out of the body
40 Check for Understanding:
• What is the difference between metabolism and metabolite?
41 Day 3 -Essential Questions
• What samples can a forensic toxicologist use in order to determine if a toxin is present?
• What techniques do forensic toxicologist use to identify drug metabolites within a person?
https://www.youtube.com/watch?v=AIQIIZCs_uk 42 Learning Targets. I can… • SFS3c – LK6: Explain what bodily fluids are used by forensic toxicologists to identify toxins. • SFS3c – LR12: Interpret results of toxicological testing • SFS3c – LR13: Predict the toxicological technique necessary to determine the identity of a toxin • SFS3 – LK7: Explain tolerance
43 Poisoned? Where do I look?
• Ingested: stomach, intestine, and liver • Inhaled: lungs • Intramuscular: will concentrate around injection site • Intravenously: absorb directly into blood; will be found throughout body, but low in stomach/liver and high in blood stream
44 Collecting Samples • Blood – Most useful sample! Drugs stay for up to 24 hrs. – antemortem blood if possible; postmortem blood is not truly “blood” – Modern technology can reveal many chemicals and their metabolites; gives you information about what was happening at time of death
45 Collecting Samples • Urine – The good: • Easy to obtain in high concentrations • May remain up to 72 hrs – The bad: • Doesn’t show how much or when the toxin/drug was ingested • Liver – Location where most drugs are metabolized (“toxin sponge”). – Can show level of drugs moments before death 46 Collecting Samples • Stomach Contents – Digestion stops at death – Contents removed, washed, and tested. – Doesn’t relate to how much was in the blood • Vitreous Humor – Liquid of the eyeball – Resistant to decay; shows chemicals long after other organs 47 Collecting Samples • Hair • Grows at a constant rate (~1.3 cm/month) • Absorbs heavy metals; provides a time line • Takes ~5 days to get into core of hair shaft
Potential Pitfalls to Analysis: • Racial variability in absorption? • Environmental exposure? • Insects – Drugs accumulate (bioaccumulation) in insects that feed on dead bodies
48 Non-biological submissions • Used to direct analysis of body fluids • May indicate class of substances that may have been ingested, inhaled or injected • Examples: – Containers found at the scene – Syringes – Unidentified tablets or liquids
Will they be looking for the same chemicals as in the body?
49 Drug Stability • breakdown of drugs may occur after death and during storage – Cocaine Benzoylecgonine (Hydrolysis) – LSD degradation due to light sensitivity • knowledge of a drug’s stability is necessary to interpret concentrations • evaporation of volatiles – Ethanol, CO, cyanide, toluene, other alcohols
50 Toxicological Testing
• Detect trace amounts of drugs in the blood, urine, and body tissues with: – thin layer chromatography, – gas chromatography, and – immunoassay techniques • Confirmation is achieved using GC/MS.
51 Toxicological Testing
• Immunoassay—measures the level of antibodies produced in response to antigens (poisons) entering the bloodstream
• https://www.youtube.com/watch?v=RRbuz3VQ100
52 Toxicological Testing • Reinsch test—for heavy metal poisoning – Certain metals dipped in hydrochloric acid produce a silver-colored coating on copper • atomic absorption spectrophotometry — identifies the specific metal – (confirmation test!) • Blood gas screenings — detects level of CO in the blood stream
53 Interpretation
54 Levels of drugs in the body:
• Normal – Level expected in the normal population
• Therapeutic – Level a doctor wants a patient to reach on prescription medicine
55 Levels of drugs in the body: • Toxic – A level that may cause harm (nausea, vomiting, etc.) • Lethal – Level that consistently causes death
56 Interpretation
Therapeutic, toxic or fatal? How do you know?
• Compare measured blood concentrations with concentrations reported in scientific studies. • Consider case history: – Symptoms observed by witnesses? – Tolerance of the individual to the drug
57 Tolerance
• Need more drug/chemical to produce effects • Metabolic Tolerance: body produces more enzymes to remove drugs • Functional tolerance: person has fewer visible signs of intoxication, although blood concentration doesn’t change
58 How did the person die?
• Medical examiner must make final determination, but a toxicology report is necessary – Is a drug or poison present? What substance? – How much of the substance is present? Is its concentration in the body sufficient to cause death? – How was the drug/poison administered?
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