Toxicologic Course - Health - Lecture Slides, Slides of Public Health

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Epidemiologic Side

of Toxicology

(6th of 10 Lectures on Toxicologic Epidemiology)

Taken in the early ’90s, when desktop computers were still a luxury.

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: 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

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: 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.

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

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.