Toxicology Principles and History

Definition of Toxicology

• Toxicology is the study of the adverse effects of chemical, physical, or biological agents on living organisms and ecosystems, including the prevention and amelioration of these adverse effects.

Scope of Toxicology: Different Branches

• Biomedical:

  • Mechanisms of action
  • Effects of exposure
  • Understanding biological responses through model toxic compounds

• Public Health:

  • Recognition and identification of hazards
  • Occupational exposure
  • Development and use of pesticides

• Regulatory:

  • Development of exposure standards
  • Detection methods

• Environmental:

  • Chemical effects on plants, animals, and ecosystems
  • Development of antidotes and treatments
  • Recognition of exposure

Scope of Toxicology: How We Got Here

• Science: Observational and data-gathering

• Art: Utilization of data to predict outcomes in humans based on in vitro and in vivo studies

• Creative Thinking: Determining the next hypothesis and designing experiments to answer posed questions

Facts vs. Predictions

• Facts are proven observations
• Predictions are based on probabilities, and do not hold the same scientific weight as facts.
• Toxicologists should be careful not to confuse these two concepts when speaking publicly.

Historical Background of Toxicology

• Toxicology dates back to the earliest humans
• Poisons played a significant role in human history, often due to negative human factors such as:
  • Lack of information/ignorance
  • Carelessness/untidiness
  • Anger leading to deliberate poisoning

History of Toxicology - Antiquity

• Humans have a long history of using poisons:
  • Hemlock (Greek capital punishment)
  • Aconite (Chinese poison arrows)
• Milestones:
  • Dioscorides, a Greek physician, classified poisons for Nero, including descriptions and drawings. This was a standard text for 1600 years.
• Toxicology during this time primarily focused on poisoning (suicide, state-sanctioned and personal use); this also led to antidotes development, like emetics (e.g., to induce vomiting after poisoning)

Most Known Historical Figures in Toxicology

• Dioscorides: First classification of poisons, use of emetics in treatment.
• Paracelsus: "All substances are poisons; there is none which is not a poison. The right dose differentiates a poison from a remedy." This established the basic principles of pharmacology, toxicology, and therapeutics; and investigation of dose-response relationships
• King Mithridates VI of Pontus: Experimented on criminals and himself, drinking a poison cocktail (36 ingredients) to prevent political enemies from poisoning him.

Further Toxicology History (Roman Times, Medieval Era)

• Significant poisonings in Rome led to a law in 82 BC making poisoning illegal, and later extending to negligent drug dispensers.
• Maimonides: Developed the concept of bioavailability, noting that the form of a toxicant (e.g., what one consumed before) influences its availability in the body. Factors like milk, butter, and cream delay intestinal absorption.
• Renaissance Italy: Poisoning was commonplace, with figures like Toffana and Hieronymus Spara. The use and effects of toxicants were investigated by figures like Catherine de Medici.
• 1775: Role of soot in scrotal cancer.
• 1825-1880: Synthesis of chemical warfare agents (phosgene, mustard gas), and a dramatic increase in new organic compounds without the necessary safety testing.

History of Toxicology - Age of Enlightenment

• Paracelsus: Focused on the single toxic agent.
• Fundamental Contributions: Experimentation is essential to understand responses, therapeutic vs. toxic properties. A degree of chemical specificity exists, which can be partially ascertained through dose investigation.
• Seminal texts:
  • On the Miners' Sickness: Paracelsus
  • Discourse on the Diseases of Workers: Bernardino Ramazzini, established norms for occupational medicine, focusing on miners, midwives, printers, weavers, and potters.
• Orfila (1787-1853): Introduced autopsy material for legal poisoning proof
• Magendie (1783-1855): Detailed absorption and distribution of compounds in the body.

20th Century

• Paul Ehrlich: Developed staining techniques to study cells and tissues, understanding of how toxicants influence living organisms.

• Rachel Carson: Alerted the public to the dangers of pesticides in the environment.

The Dose Makes the Poison

• An apparently nontoxic chemical can be toxic at high doses
• Highly toxic chemicals can be life-saving in appropriate doses.

Lethal Doses of Common Chemicals (Rats)

• Approximate lethal doses for common chemicals like sugar, alcohol, salt etc were calculated from rat data, scaled for a human of 160 lbs.

Toxicology: What Toxins Are Made From

• Toxicants: Specific poisonous chemicals produced by plants, animals, or bacteria.

  • Phytotoxins: Plant-derived
  • Zootoxins: Animal-derived
  • Bacteriotoxins: Bacteria-derived

• Xenobiotics: Man-made substances and/or produced by another organism, but not naturally occurring in the human body

Other Historical Mentions

• 2700 B.C.: Chinese journals on plant and fish poisons.
• 1900-1200 B.C.: Egyptian documents describing medicinal and poisonous recipes.
• 800 B.C.: Indian Hindu medicine with notes on poisons and antidotes.
• 50-100 A.D.: Greek physicians classifying plant, animal, and mineral poisons.
• 50-400 A.D.: Romans used poisons for executions and assassinations, including incidents like the death of Socrates by hemlock.
• 1200 A.D.: Maimonides wrote a medical aid book on poisons and antidotes