Lecture 1 Flashcards
What occurred during the stone age?
-The earth was in an Ice Age
-They used small group hunting for survival
-Made the Acheulean stone tool (hand axe)
Earliest “Toxicology”
-Ancestors knew some plant and animals as harmful and others as safe from experience and told this from generation to generation
-Snakes to be venomous and used this for hunting, warfare, and assassination for power
Metal age was in what age?
Ancient age in 3200-600 BC
Copper Age
-in the Ancient age
-Oldest technology was copper smelting
-pottery kilns had high temperature to melt copper
Bronze Age
-An alloy of copper with tin
-Material for making tools (advancement from stone because of its mechanical strength and ductility and it could be cast in molds to make shapes)
Iron Age
-Replaces bronze because stronger, lighter, and cheaper.
Metal age main characteristics:
-clay pottery
-produce tools and food to stay alive
-form villages to live in a community
-sedentary towns, the birth of civilization
-Metals are the fabric of human history and the engine of toxicology
Invention of writing
-Ancient age
-3000 BC
The Ebers Papyrus
-An Egyptian medical papyrus (textile writing fiber materials for writing) of herbal knowledge 1500 BC
-Kept in Leipzig, Germany
-Recorded poisons and poisonings: hemlock, aconite, opium, metals (arsenic, lead, copper, antimony)
Poisons from Aconite
-A plant poison in backyard
-highly toxic cardiotoxins and neurotoxins after ingestion or consumption
-Patients present predominantly with a
combination of neurological, cardiovascular, and
gastrointestinal features
-Treatment: amiodarone and flecainide
Classical period of the Greeks
-Ancient time
-Socrates, Plato, and Aristotle
-Gold and silver invented
-Hippocrates: Father of Medicine (concept of overdose
-Book of Job: the term of Toxicology comes from this, poison arrows
Roman Empire
-Ancient age
-19 greatest inventions: Roman numerals, surgical tools, sewage
system/sanitary management, water
supply, laws and orders …
-Codex: the first bound book for
Julius Caesar (100 BC – 44 BC)
Han Dynasty
-Ancient age
-Paper was invented in China
-Desire for immortality – Alchemy:
The 1st Emperor Qin Shi Huang
(259 BC - 210 BC) died of mercury
Alchemy
- The first metal toxicity case
-pills of immortality: lead, mercury, iron . . . - Metals, plant and animal toxins recognized and
recorded.
-Arsenic
King Mithridates Death
-100 BC Roman Republic’s enemies
-Ruler of the Kingdom of Pontus
-After assassination of his father in 120 BC,
he started regularly ingesting sub-lethal
doses of the same poison (mainly arsenic)
that killed his father and developed the
immunity to poisons
-The night before the battle, the assassin
added the dose to his wine. But next day on
the battle ground, the Romans were
astonished that he was alive. Mithridates
defeated Roman army again.
-After Pompey defeated him in Pontus in 66 BC, King
Mithridates fled back home trying to raise a new army.
* However, the local nobles rebelled against his rule.
* He was desperate and attempted suicide by poison; but
his attempt failed because of his immunity to poisons.
* … and his loyal guide had to hand him a sword…
“Lex Cornelia”, a Roman Law (82 BC)
-1st Law against Poisoning in Roman History
-In 82 BC, in an attempt to stem what was
becoming an epidemic of large-scale arsenic
poisonings, the Roman dictator and
constitutional reformer Lucius Cornelius Sulla
issued the Lex Cornelia, the first law in the
western civilization against poisoning.
* The Law aimed at the punishment of murderers,
poisoners, abortionists, human sacrifice, and
malign magicians.
Meideval Age
Medieval England:
-People were punished for food poisoning
-Seller of adulterated food> immersed in a dirty pond
-Violating butcher> paraded with face close to horse’s tail
Chinese Tang Dynasties
-Serve of toxic food> flogged or spanked 90 storkes
- Spoiled foor sold to another> banished 1 year
-Person died> hanged
Turkey or Ottoman Empire
-Baker selling adulterated bread →
had an ear cut off and nailed to his
doorpost
* Wine maker who adulterated wine
→ condemned to drink 6 quarts of
his own product (usually fatal)
Renaissance
-Art and science: : astronomy, physics, biology, and
anatomy …
-Paracelsus: father of toxicology
-Ellenbog recorded toxicity of mercury and lead exposures in goldsmithing (studies of these metals started)
Paracelsus
-Father of Toxicology
- He encouraged using experimental animals to study both
beneficial and toxic chemical effects.
* He advocated the use of inorganic salts, metals, and
minerals for medicinal purposes.
* To cure a disease caused by poisons, a substance of
similar nature but the opposite effect should be
administered, hence, the concept of antidote.
Mercury as a therapeutic drug for treatment of
syphilis
Therapeutic effect (Dose-Response relationship)
dose that will be most effective
Does-Response relationship: The intensity of a response to a given amount of chemicals
Paracelsus: “All substances are poisons; there is none
which is not a poison. The right dose
differentiates poison from a remedy.”
Time Course of Poisons in the Body
-The time course is how the body
processes a chemical via its
absorption, distribution, metabolism and
elimination (ADME).
Toxicodynamics
Science of studying drug / poison effects on human health
Toxicokinetics
study of the time course of the effects of a chemical on the body
Bernardino Ramazzini
-Father of Occupational Disease
-Wrote on the disease of workers
-focus on prevention rather than treatment of disease
Thomas Savery
- 1st Industrial revolution
-invented the steam engine in England
Dr. John Couper
1st case of manganism was described by him in 1837
-Two workers in scotland involved in grinding of manganese ore developed paraplegia (worst in lower extremities)
-Birth of descriptive toxicology (describing signs and symptoms in great detail)
Mathieu Orfila
-A Spanish physician in the French court
-The first to use autopsy material for chemical analysis as the legal proof of poisoning
-Birth of Forensic Toxicology
-Established workers Insurance Law in germany, england, and US
Invention of the Atomic Absorption Spectrophotometry
-First analytical technique for metal analysis and remains widely used to this day
- Established by Robert Bunsen and Gustav Kirchhoff
- Clinical analysis of metals in biological fluids and tissues
- Toxicology study and safety evaluation of metal toxicities in humans, animals, and plants
-Metals in water, soil, and air
-Pharmaceutical manufacturing of metal-based drugs
Invention of the Periodic Table
Dimitri Mendeleev arranged chemical elements by atomic mass and predicted the discovery of other elements by leaving spaces on the table for them
Contemporary age (1898 to present)
-2nd industrial Revolution
-1913: Henry Ford built the assembly line
for mass production and initiated the 2nd Industrial Revolution
- All medicines sold in the U.S. had no prescriptions (people died)
Poison Squad
-Consumer protection agency in 1900 after people were dying from medicines sold with no prescriptions
-Dr. Harvey Wiley: Father of the FDA. Professor at Purdue in 1874 and state chemist of indiana (Pure food and Drug act and first commissioner of the FDA)
Regulatory Toxicology
The original Pure Food and
Drugs Act is passed by Congress and
signed by President Theodore
Roosevelt.
* It prohibited interstate commerce in
misbranded and adulterated foods,
drinks and drugs.
* Birth of Regulatory Toxicology.
Nikola Tesla
-First worked in Edison Lab in 1884
-Later made his own lab in NYC and invented alternating current (AC)
-accidentally took an X-ray image
-discovered rotating magnetic field which enabled the development of MRI
Manganese induces what?
Parkinsons
-movement disorder
-Damage brain striatal function
XRF spectroscopy
-Vladimir Veksler made synchrotron
-a type of particle accelerator that produces extremely bright and intense beams of light
* Allow for a “true” imaging of specific
metal content in tissues.
- Used in Toxicology: Helps show lead (Pb) formation called amyloid plaques in the brain of Alzheimers patients
Cell Death: Necrosis
Programed cell death mechanisms are what?
1) Apoptosis
2) Autophagy
The 3rd industrial revolution
-Characterized by internet, automation and
digitization through the use of electronics
and computers.
-Increased the power of risk assessment and predictive toxicology
Risk Assessment &
Predictive Toxicology
-Using the concept of
“Reference Dose (RfD)”
to predict the safety of a
potentially toxic chemical
* Frequently used in safety
assessment and approval
in industry and
governmental regulation
Computational and Predictive Toxicology
- Integrates information and data from multiple sources to develop mathematical and computer based models to better understand and predict adverse health effects caused by chemicals, such as environmental pollutants and pharmaceuticals
Mechanistic Toxicology
branch of toxicology that focuses on understanding the biological mechanisms by which chemicals or other substances cause harmful effects on living organisms.
-Biological or biochemical process that lead to toxicity.
