TOX Lecture 3

Historical Foundations

• Sir Percivall Pott ( $1714-1788$ ): first to show an environmental carcinogen can cause cancer.

• Carl W. Scheele ( $1742-1786$ ): isolated and characterized many important chemicals and poisons.

• Friedrich Wilhelm Sertürner ( $1783-1841$ ): isolated morphine.

• Francois Magendie ( $1783-1885$ ): described absorption and distribution of compounds in the body.

• John Hill ( year shown: 1761 ): linked tobacco (snuff) to cancer.

• James Marsh ( $1794-1846$ ): invented the Marsh test for arsenic detection.

• Mathieu Joseph Bonaventure Orfila ( $1787-1853$ ): founder of toxicology; Traité des poisons (1814–1815).

Industrialization and Toxicology Gaps

• Late 1800s (~ $1880$): boom in organic chemical synthesis; many new compounds enter market.

• No industry-wide toxicity testing.

• Occupational risk example: Aniline dye workers and radium dial-watch painting; brushing and licking to pull lines increased exposure risk.

Chemical Warfare and Public Health History

• Chlorine as first killing agent used by German military; BASF, Hoechst, Bayer produced chlorine; Fritz Haber collaborated; 1825 synthesis of phosgene and mustard gas (chemical warfare).

• Prohibition era ( $1920-1933$ ): moonshine production with lead and/or methanol contamination.

• Gerhard Schrader ( $1903-1990$ ): accidental discovery of nerve agents (sarin, tabun, soman, cyclosarin) while seeking insecticides; later used in WWII; called the "father of the nerve agents".

Hazardous Waste and Environmental Contamination

• CAUTION: HAZARDOUS WASTE SITE; DIOXIN CONTAMINATION; Times Beach, MO (Route 66 through Times Beach).

• Lessons: improper waste management and contamination risks to communities.

Cold War and Assassination Toxins

• Georgi Markov ( killed in $1978$ ): KGB-designed pen-like device delivering ricin pellets.

• Ricin toxicity and assassination cases illustrate non-weaponized toxins used for covert harm.

Notable Toxins: Symptoms and Public Incidents

• Ricin symptoms (ingested/inhaled): $abdominal ext{ pain}, ext{ vomiting}, ext{ diarrhea (often with blood)}$; hemorrhages in intestines; necroses in liver/kidneys; severe dehydration; thirst; throat burning; headache; death by hypovolaemic shock; temperature drop before death; shivering.

• 1982 Chicago cyanide poisoning: led to tamper-proof packaging for medicines.

• Bhopal Disaster ( $1984$ ): release of $Methyl ext{ isocyanate}$; thousands killed, hundreds of thousands injured.

• Tokyo Subway Sarin Attack ( $1995$ ): 12 dead, ~6,000 injured; perpetrators: Aum Shinrikyo.

Modern Poisoning and Risk Signals

• Viktor Yushchenko poisoning ( $2004$ ): widely reported as dioxin (TCDD) poisoning.

• Notable recent risk signals:

  • Risk found in newer antipsychotic drugs (The New York Times, $2009$).

  • Vicks VapoRub linked to infant breathing problems.

  • Pet food recalls due to melamine adulteration.

  • Toy recalls due to lead paint.

Reference Frameworks

• A Small Dose of Toxicology, Steven G. Gilbert

• Tox 201: Poisons, People and the Environment, Stephen Graham Casarett and Doull’s Toxicology (eds. Mary Amdur, John Doull, Curtis Klaassen)

• The New York Times; CNN News Reports