Chapter 13

Toxicology: Drugs, Toxic Substances, and Forensic Chemistry

  • Course: Chem 113, Prof. J.T. Spencer

Introduction to Toxicology

  • Paracelsus Quote: "What is there that is not a poison? All things are poison and nothing without poison. Solely the dose determines that a thing is not a poison." (1493-1541)

Overview of Drugs and Toxins

  • Definitions:

    • Drugs: Natural or synthetic compounds used for physiological (and possibly psychological) effects.

    • Medicinal Uses: To correct or help some physiological or psychological problem.

    • Drug Abuse: Chemicals taken for unintended uses (“off-label”) or uncontrolled use (e.g., alcohol addiction).

    • Cuts across socio-economic levels.

    • Greater than 75% of forensic investigations involve drug use.

    • Not victimless crimes.

Forensic Toxicology

  • Definition: The study of drugs and poisons and their adverse effects on the human system.

  • Subfields:

    • Pharmacodynamics: How a drug affects an organism.

    • Pharmacokinetics: How the organism affects the drug.

Outline of Topics

  • Medicinal Chemistry:

    • Toxins

    • Poisons

  • Drug Discovery and Development

  • Drugs of Abuse (Illegal Drugs):

    • Drug Definitions and Types

    • Drug Laws

    • Drug Dependence

    • Drug Testing and Identification

  • Alcohol Toxicology

Key Toxicological Terms

  • Dose: The amount of substance that enters the body.

  • LD50: Dose necessary to kill ½ of the population.

  • Acute Toxicity: Effects are immediate.

  • Chronic Toxicity: Effects occur over an extended time.

  • Species Specificity:

    • Example: Dioxin - polychlorinated organic compounds; toxicity varies with species.

    • LD50 Examples:

      • Guinea Pig: 0.0006 mg/kg

      • Rabbit: 0.115 mg/kg

      • Hamster: 3.5 mg/kg

      • Monkey: 0.07 mg/kg

LD50 Calculations

  • Cyanide (for a 150 lb human - approximately 70 Kg):
    (70 ext{ Kg})(10 ext{ mg/Kg}) = 700 ext{ mg} (0.70 ext{ g})

  • Nicotine (from cigarettes):
    (70 ext{ Kg})(2 ext{ mg/Kg}) = 140 ext{ mg} (0.14 ext{ g})
    Note: 1 cigarette = ~2 mg Nicotine.

  • Ethanol:
    (70 ext{ Kg})(1000 ext{ mg/Kg}) = 70,000 ext{ mg} (70 ext{ g})

Effect of Body Weight on LD50

  • Ethanol LD50 dose example:

    • 150 lb. Human: Approximately 70 g

    • 40 lb. Dog: Approximately 20 g

LD50 Values of Various Substances

  • Substance and Corresponding LD50:

    • Aspirin: 1750 mg/kg

    • Ethanol: 1000 mg/kg

    • Morphine: 500 mg/kg

    • Caffeine: 200 mg/kg

    • Heroin: 150 mg/kg

    • Lead: 20 mg/kg

    • Cocaine: 17.5 mg/kg

    • Cyanide: 10 mg/kg

    • Nicotine: 2 mg/kg

    • Strychnine: 0.8 mg/kg

    • Batrachotoxin: 0.002 mg/kg

Right to Know Laws

  • Materials Safety Data Sheets (MSDS): Provides specific toxicological, chemical, and physical data about a compound.

    • Includes information on:

    • Physical Properties and Names

    • Chemical Reactivities

    • Incompatibilities

    • Safe Handling

    • Toxicology (symptoms and means of exposure)

    • Safety and First Aid

    • Additional Information

Example of an MSDS: NICOTINE

  • Chemical Names and Formulas:

    • (S)-3-(1-Methylpyrrolidin-2-yl)pyridine

    • CAS #54-11-5

    • Molecular Mass: 162.2

Acute Hazards and Prevention Methods:

  • Fire: Combustible, gives off irritating or toxic fumes in a fire.

  • EXPLOSION: Above 95°C explosive vapor/air mixtures may form.

  • Exposure Risks:

    • Inhalation: Burning sensation, nausea, vomiting, convulsions, etc.

    • Skin: May be absorbed, resulting in redness, burning sensation.

    • First Aid:

    • Fresh air, rest, and refer for medical attention.

    • Protective gloves, clothing, and washing instructions.

Poisons

Types of Poisons:

  • Intentional or Accidental

  • Corrosive Poisons: Substances that destroy tissue outright.

    • Examples:

    • Sulfuric Acid (H2SO4): Can be fatal; causes tissue dehydration.

    • Hydrochloric Acid (HCl)

    • Sodium Hydroxide (NaOH): Causes tissue death by hydrolysis of peptide bonds.

Warning Properties of Corrosive Poisons:

  • Corrosive Toxins:

    • Interact with body sensory systems to alert for exposure (e.g., ammonia causing choking).

    • Some lack warnings (e.g., HF, which destroys tissue/bone without immediate pain).

Metabolic Poisons

  • Definition: Affect biochemical mechanisms.

  • Examples:

    • Carbon Monoxide (CO): Colorless and odorless gas that binds to hemoglobin, preventing oxygen transport.

    • Converts 60% of hemoglobin to carboxyhemoglobin when inhaled in 0.1% concentration.

    • Cyanide (CN-): Fast-acting poison that causes asphyxiation by hindering oxygen utilization.

    • Found in certain fruits, and is derived from industrial processes.

    • Antidote: Large amounts of thiocyanate can be effective.

Examples of Poisoning and Their Sources

  • Cyanide Poisoning: Can occur through ingestion of various seeds and pits (e.g., wild cherry syrup, peach pits).

  • Arsenic Poisoning: Commonly found in pesticides, shrimp, and treated wood.

    • Mechanism: Reacts with SH groups of enzymes and accumulates in the body.

  • Mercury Poisoning: Associated with fluorescent lamps, dental amalgams, leading to neurological issues.

  • Lead Poisoning: Related to historical lead plumbing and paints, affecting mental health and contributing to neurological conditions.

Drug Discovery and Development

Origins of Drugs

  • Many drugs originate from therapeutic chemicals later used off-label.

Discovery Methods:

  • Traditional Medicines (ethnopharmacology)

  • Serendipitous Discovery

  • Targeted Discovery

  • Modifying Known Compounds

Example: Aspirin

  • Derived from willow bark, isolated compounds showed medicinal use.

  • Significant side effects from the acidic form led to modifications for safer use.

Drug Development Process

  • Costs between $800 million (2003) and $1.7 billion (2009).

  • Timeline: Up to 15 years to develop a drug from discovery to approval.

  • Only 1 in 1,000 compounds in preclinical testing reach human trials; only 20% of those are approved.

Stages in Drug Development:

  1. Synthesis and Extraction

  2. Screening and Testing

  3. Toxicology and Safety Testing

  4. Clinical Evaluations (Phases I, II, III)

  5. Regulatory Review and Approval

Active Areas in Targeted Drug Discovery

  • Synthesis and modification of functional groups to create active pharmaceutical ingredients (APIs) with reduced side effects.

Controlled Substances Act (CSA) of 1970

  • Legal framework regulating drug abuse and distribution. Classifies drugs into schedules based on abuse potential and medical use.

    • Schedule I: High potential for abuse, no accepted medical use. (e.g., Heroin, LSD)

    • Schedule II: High abuse potential, accepted medical use with severe restrictions. (e.g., Morphine, Methamphetamines)

    • Schedule III: Moderate potential for abuse, accepted medical use. (e.g., Anabolic steroids)

    • Schedule IV & V: Lower potential for abuse compared to Schedules I-III.

Types of Abused Drugs

  • Narcotics: Pain relief and sedative properties (Opioids, Morphine, Heroin).

  • Hallucinogens: Alter perception and mood (LSD, PCP, MDMA).

  • Depressants: Decrease CNS function (Alcohol, Barbiturates).

  • Stimulants: Enhance activity and alertness (Cocaine, Amphetamines).

Alcohol

Overview

  • Alcohol is the most abused drug; more related deaths than any other substance.

  • Historical significance: used for thousands of years, e.g., wine production in ancient Greece and Rome.

Alcohol Types:

  • Methanol (CH3OH): Toxic, with LD50 = 428 mg/kg.

  • Ethanol (C2H5OH): Safe at lower doses, with LD50 = 7060 mg/kg.

  • Propanol (C3H7OH): Toxic, with LD50 = 3600 mg/kg.

Alcohol Metabolism

  • Absorption primarily in the stomach and small intestine; rapid increase in blood alcohol concentration (BAC). Factors influencing absorption include food intake and physical activity.

  • Ethanol diffuses throughout the body, crossing the blood-brain barrier and placenta.

  • Individual responses to alcohol influenced by genetics, previous drinking history, environment, and co-consumed substances.

Alcohol Effects on the Brain

  • Alcohol affects various brain regions, leading to impaired cognitive function and motor skills.

  • Notable grading of intoxication levels (BAC):

    • Mild Intoxication: 0.050% w/v – Warm feeling, flushed skin, impaired judgment.

    • Obvious Intoxication: 0.100% w/v – Significant impairment, slowed reflexes.

    • Extreme Intoxication: 0.250% w/v – Severe cognitive and motor impairments.

    • Coma/Death: 0.350%+ w/v – Likelihood of coma and death.

Ethanol Testing and Legal Aspects

Testing Methods

  • Specimen Acquisition: Breath, blood, or urine samples used to assess BAC.

  • Field sobriety tests to indicate impairment.

Legal Considerations

  • Implied consent for BAC testing; penalties for refusal.

  • Various legal limits for BAC dependent on type of driver (e.g., standard vs. commercial).

Conclusion

  • Understanding the mechanisms of drugs and poisons is crucial for public health and safety. The study of toxicology informs legal policies, medical practices, and forensic investigations.