Lecture 3 Flashcards
Describe the environmental health paradigm.
Explain the steps of the toxicological paradigm.
What is toxicology?
The study of adverse effects of chemical, physical, or biological agents on living organisms and the ecosystem, including the prevention and mitigation of such adverse effects.
We study toxicology to assess risk and delineate causes of disease.
What are the risk assessment process steps, and which are specifically associated with toxicology.
- problem formation
- hazard identification (t)
- dose-response assessment (t)
- exposure assessment (t)
- risk characterization
What is hazard identification?
2nd step in risk assessment, it is a literature review to identify health effects of exposure to the hazard.
What is dose-response assessment?
3rd step in risk assessment, it quantifies dose-response relationships. A dose-response relationship is one in which increasing levels of exposure are associated with either an increasing or a decreasing risk of the outcome.
What is exposure assessment?
4th step in risk assessment, it estimates human/ecological doses. Exposure assessment is “the process of estimating or measuring the magnitude, frequency, and duration of exposure to an agent(the cause of a disease), along with the number and characteristics of the population exposed. Ideally, it describes the sources, routes, pathways, and uncertainty in the assessment.”
Describe toxicology vs. pharmacology
Describe toxicants vs. toxins
Toxicants: Toxic substances that are manmade or result from human (anthropogenic) activity
Toxins: Usually refer to a toxic substance made by living organisms including reptiles, insects, plants, and microorganisms. (like mold)
Give some examples of adverse health effects
How are experimental toxicology responses studied/measured?
What is principle 1 of toxicology?
Toxic action of a substance is a consequence of the physical/chemical interaction of the active form of that substance with a molecular target within the living organism.
What is principle 2 of toxicology
Toxicity is related to the concentration of the active form of the toxicant at the site where the molecular targets are located.
What are the issues with dose response?
Involves extrapolation of animal or cell culture data to human exposure levels
Is it association (epidemiology) vs. cause/effect
Can toxicants cause disease?
No, they increase one’s risk for developing disease.
Name some exposure points.
What is bioavailability?
The fraction that can be taken up by the organism (internal exposure) in relation to the total amount of the substance available (external exposure).
Describe external to internal exposure.
What are the steps in toxicokinetics?
Absorption
Distribution
Metabolism (Biotransformation)
Storage
Excretion
What are routes of internal exposure?
How do xenobiotics (foreign) chemicals enter the body?
- If a xenobiotic is soluble in organic (nonpolar) solvents, it will easily cross the intestinal membrane (which is comprised of lipids, i.e. nonpolar)
- If a xenobiotic is polar/ionic (more soluble in water), it often mimics the properties of a nutrient and crosses the intestine through a transporter (e.g. iron transporter whatevs). Referred to as the Trojan horse mechanism.
- Almost all nutrients require a transporter.
How does distribution/circulation mean?
How are toxicants excreted from the body?
urinary excretion
exhalation
biliary excretion via fecal excretion
milk
sweat
saliva
How are toxicants stored in the body?
Adipose tissue, so rapid mobilization of the fat (starvation) can rapidly increase blood concentration
Bone, chemicals mimic calcium so loss of bone spills metals into blood
Explain biotransformation. (metabolism)
Metabolism is the process by which the administered chemical (parent compounds) are modified by the organism by enzymatic reactions.
What are single nucleotide polymorphisms (SNPs)?
The most common type of genetic variation among people. They affect absorption, distribution, biotransformation, excretion, storage, and toxicodynamics
How can half-life help to assess internal exposure?
How is blood distributed in the body?
Name some factors that affect metabolism.
age
gender
race
genetics
diet
latitude
health
socioeconomic status
What are biomarkers?
A biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition.
Biospecimens for internal exposure: blood, urine, hair
Biological event: PSA (prostate specific antigen), polyps (colon), bad cholesterol, LDL (heart)
