Lecture 3

Question 1

Describe the environmental health paradigm.

Answer 1

Question 1

Explain the steps of the toxicological paradigm.

Answer 1

Question 2

What is toxicology?

Answer 2

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.

Question 3

What are the risk assessment process steps, and which are specifically associated with toxicology.

Answer 3

1. problem formation
2. hazard identification (t)
3. dose-response assessment (t)
4. exposure assessment (t)
5. risk characterization

Question 4

What is hazard identification?

Answer 4

2nd step in risk assessment, it is a literature review to identify health effects of exposure to the hazard.

Question 5

What is dose-response assessment?

Answer 5

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.

Question 6

What is exposure assessment?

Answer 6

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.”

Question 7

Describe toxicology vs. pharmacology

Answer 7

Question 8

Describe toxicants vs. toxins

Answer 8

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)

Question 9

Give some examples of adverse health effects

Answer 9

Question 10

How are experimental toxicology responses studied/measured?

Answer 10

Question 11

What is principle 1 of toxicology?

Answer 11

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.

Question 12

What is principle 2 of toxicology

Answer 12

Toxicity is related to the concentration of the active form of the toxicant at the site where the molecular targets are located.

Question 13

What are the issues with dose response?

Answer 13

Involves extrapolation of animal or cell culture data to human exposure levels

Is it association (epidemiology) vs. cause/effect

Question 14

Can toxicants cause disease?

Answer 14

No, they increase one’s risk for developing disease.

Question 15

Name some exposure points.

Answer 15

Question 16

What is bioavailability?

Answer 16

The fraction that can be taken up by the organism (internal exposure) in relation to the total amount of the substance available (external exposure).

Question 17

Describe external to internal exposure.

Answer 17

Question 18

What are the steps in toxicokinetics?

Answer 18

Absorption
Distribution
Metabolism (Biotransformation)
Storage
Excretion

Question 19

What are routes of internal exposure?

Answer 19

Question 20

How do xenobiotics (foreign) chemicals enter the body?

Answer 20

• 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.

Question 21

How does distribution/circulation mean?

Answer 21

Question 22

How are toxicants excreted from the body?

Answer 22

urinary excretion
exhalation
biliary excretion via fecal excretion
milk
sweat
saliva

Question 23

How are toxicants stored in the body?

Answer 23

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

Question 24

Explain biotransformation. (metabolism)

Answer 24

Metabolism is the process by which the administered chemical (parent compounds) are modified by the organism by enzymatic reactions.

Question 25

What are single nucleotide polymorphisms (SNPs)?

Answer 25

The most common type of genetic variation among people. They affect absorption, distribution, biotransformation, excretion, storage, and toxicodynamics

Question 26

How can half-life help to assess internal exposure?

Answer 26

Question 27

How is blood distributed in the body?

Answer 27

Question 28

Name some factors that affect metabolism.

Answer 28

age
gender
race
genetics
diet
latitude
health
socioeconomic status

Question 29

What are biomarkers?

Answer 29

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)