The 6th lecture of the series Epidemiologic Side of Toxicology by sammyc2007

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									Epidemiologic Side
  of Toxicology
    (6th of 10 Lectures on
  Toxicologic Epidemiology)


Michael H. Dong
 MPH, DrPA, PhD
                      readings
Taken in the early ’90s, when desktop computers were still a luxury.
   Learning Objectives
• Appreciate the importance of the
  epidemiologic side of toxicology.
• Study the epidemiologic relevance
  through three historical events.
• Learn the impact of epidemiology,
  which is dynamic, case-dependent,
  and often tremendous.
Performance Objectives
• Able to describe the toxicologic
  course of the three historical events
  presented.
• To characterize the epidemiologic
  side of these courses and events.
• To outline the purpose as well as
  the principles of presenting the
  three toxicologic events.
Three Case Studies for
the Epidemiologic Side
    of Toxicology:
1. Jamaica Ginger Epidemic
2. London Smog of 1952
3. Multistage Model of
   Carcinogenesis
     Ginger Paralysis:
        Syndrome & Cause
• Characterized by ataxia, muscular
  weakness, unsteady gait, flaccid
  paralysis of the legs.
• Also known as jake leg, wrist drop,
  and foot drop.
• Caused by exposure to TOCP, with
  delayed onset of 1 to 3 weeks.
Ginger Paralysis: History
       and Toxicity
• The syndrome known for a century;
  and later, as ginger paralysis due to
  its first major episode in the USA.
• TOCP is the most toxic isomer of
  TCP; both, like some other OP, can
  induce delayed neurotoxicity.
• The initial effects likely involve the
  inhibition of neurotoxic esterase.
  Ginger Paralysis: The
   Epidemiologic Side
• 20,000 cases reported in the USA in
  1930, related to consumption of illegal
  alcohol contaminated with TOCP.
• 10,000 cases reported in Morocco in
  1959, related to consumption of food
  cooked in oil contaminated with TOCP.
• The association was initiated by two
  Oklahoma doctors: Miles and Goldfain.
  Ginger Paralysis: The
   Impact of Epidemiology
• It was the first major epidemic that
  enabled Smith et al. to focus on
  TOCP as the prime suspect.
• A large number of toxicology
  studies were hence launched, along
  with U.S. EPA’s development of a
  regulatory guideline specifically for
  testing delayed neurotoxicity.
  Ginger Paralysis: The
  Lesson (and Speculation)
•Despite the Jamaica ginger episode,
 there were still numerous outbreaks
 involving cooking oil contaminated
 with TOCP.
•Delayed neurotoxicity is extremely
 specific to chemical structure.
•It was epidemiologic evidence that
 advanced the toxicology of TOCP.
 London Smog: History
    & the Epidemic
• 4,000 premature deaths, with most
  being elderly or having preexisting
  diseases, from breathing heavily
  polluted air in London in 1952.
• Smog is a mixture of smoke and fog,
  now also involving the equally irritating
  photochemical air pollution.
• Air pollution is predictable, and was
  recognized back in the Roman period.
London Smog: Toxicity
  of the Air Pollutants
• Sulfur dioxide is an upper airway
  irritant.
• Carbon dioxide is a potent asphyxiant.
• Nitrogen dioxide causes severe
  irritation of the innermost parts of the
  lungs.
• Ozone is a reactive and toxic form of
  elemental oxygen.
    London Smog: Other
  Pollutants & Newer Problems
• Other pollutants: suspended particulate
  matter (e.g., black smoke); and volatile
  organic compounds (e.g., petroleum
  benzene as an exhaust product).
• 1.6 million people may now be at risk
  from poor air quality in urban areas
  throughout the world.
• There are also areas everywhere filled
  with traffic-generated pollutants.
  London Smog: The
 Impact of Epidemiology
• The 1952 incident led to the passage of
  the British Clean Air Act of 1956.
• More epidemiologic studies have since
  been conducted to cope with air
  pollution problems and episodes.
• Also more studies on long-term toxic
  effects and on photochemical formation.
    London Smog: The
         Lesson
• The older winter smog problem in
  London and worldwide is now
  being replaced with summer smogs
  from photochemical formation.
• The adverse health effects of the
  winter or summer air pollutants
  cannot be investigated using classic
  toxicology studies alone.
 Multistage Model: The
  Course of Carcinogenesis
• Carcinogenesis is the biochemical
  process characterizing the progression
  of normal cells to neoplastic and later
  into tumor cells.
• Multistage model is a quantitative as
  well as a mechanistic theory used to
  characterize this biochemical process.
• Two of the stages basic to the model are
  presumably initiation and promotion.
  Multistage Model: The
   Underlying Theories
• In addition to being an initiator or a
  promoter, an agent initially can be a
  precarcinogen and later be transformed
  into a harmful ultimate carcinogen.
• Initiation is usually irreversible, of short
  duration, and invisible, whereas
  promotion has the opposite effects.
• As an outgrowth of the challenge to the
  single stage and the multicell theories.
 Multistage Model: The
  Epidemiologic Side
• The single stage model and the multicell
  model were found to be incompatible
  with epidemiologic data.
• Although the multistage model is based
  on a single cell theory, its development
  was driven by epidemiologic data that
  many cancer incidences increased with
  the 5th or 6th power of age (that also
  implicating latency period).
 Multistage Model: The
 Relevance and Impact
• Gaining wide acceptance due to the
  strong evidence that cancer is a single
  cell in origin.
• Useful as a quantitative tool in the
  cohort analysis of tumors induced by
  chemicals.
• Found for the large part successful in
  describing many experimental and
  epidemiologic data.
 Multistage Model: The
  Lesson & Its Utilities
• Leading to the use of more proper
  mitigation measures; and to the
  adoption by regulatory agencies for
  cancer risk assessment.
• Toxicologists using animal studies,
  without this epidemiology-based
  theory, would likely fail to elucidate
  or make fuller use of the mechanistic
  process of carcinogenesis.
   Overview of Next Lectures
      Human Exposure
      Assessment I & II
• Human exposure assessment is one of
  the key components in the health risk
  assessment.
• Lecture 7 (Assessment I) will cover the
  direct measurement methods.
• Lecture 8 (Assessment II) will focus on
  the indirect measurement methods.

								
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