TOX 300 Study Guide - Fall 2018, Comprehensive Midterm Notes - Xenobiotic, Adme, Toxicokinetics
TOX 300
MIDTERM EXAM
STUDY GUIDE
Fall 2018
L1 Introduction
Toxicology examines the adverse effects of chemicals on living organisms
Xenobiotics = foreign chemicals (drugs, by-products, natural toxins, pesticides)
Toiolog is a ultidisiplia siee that oows appoahes ad tehiues from many other
sciences
Chemical revolution (1920-1970) – major chemical advances
- In 1970, the dilution paradigm was replaced by the boomerang paradigm
o Dilution paradigm = dilution is the solution to pollution
o Boomerang paradigm = what we throw out there will come back
- Two chemicals that brought attention to the dilution paradigm: DDT & methylmercury
o DDT = bioaccumulates in the organism and works its way up the food web
o Methylmercury = byproduct in industries that uses mercury as a catalyst
Methylmercury
Organochlorines = very persistent and bioaccumulative
Thalidomide = depends when the exposure occurs
Diethylstilbestrol (DES) = potent estrogen to prevent miscarriages → daughters of users developed a
rare vaginal cancer
The dose defines the poison - Paracelsus
Toxicokinetics = disposition of a cemical in an
animal overtime
- ADME = what the od does to the
eoiotis
- Absorption, distribution, metabolism,
excretion
- Determines the DOSE
Toxicodynamics = effects of xenobiotics
- what the eoioti does to the od
- determines the RESPONSE
- learn about mechanisms
What do toxicologists do?
- Descriptive toxicologist = toxicity testing
- Analytical toxicologist = identifies toxicants in various medias
- Mechanistic toxicologist = determines modes of action of toxicants
- Occupational toxicologist = job-related exposures and effects
- Regulatory toxicologist = applied risk assessment
- Forensic toxicologist = determines cause and circumstances of death
- Clinical toxicologist = studies environmental pollutants in humans and other living organisms
- Environmental toxicologist = studies environmental pollutants in humans and other living
organisms
- Ecotoxicologist = studies environmental pollutants in an ecological context (population and
community impacts)
find more resources at oneclass.com
find more resources at oneclass.com
L2 ADME (Absorption, Distribution, Metabolism, Excretion)
Toxicokinetics = determination of the time course of disposition (ADME) of xenobiotics in the body
- What the od does to the eoioti
- Determines the concentrations (dose) of xenobiotic at its site(s) of action, and thus is linked to
the intensity of biological effect
*Most xenobiotics have to enter the bloodstream to be distributed throughout the body
Absorption
- Animal cell membranes are phospholipid bilayers
- The lipophilicity (lipid solubility) of a xenobiotic is the most important factor allowing it to
diffuse across cell membranes
- Size and charge of a molecule are also very important
**Xeoiotis a hith a ride ith these trasporters to eter a ell
1. Passive (simple) diffusion = follows the concentration gradient
a. Very small hydrophilic chemicals
▪ E.g. ethanol → aqueous pores in the membrane – paracellular diffusion
▪ Paracellular diffusion = transfer of substances across an epithelium by passing
through the intercellular space b/w the cells
b. Lipophilic organic molecules
▪ E.g. organochlorines (DDT)
▪ How to determine lipophilicity? Octanol:water partition coefficient (Kow)
• Water is polar, octanol is lipophic
• DDT: log(Kow) = 6 → means that 1 water: 1,000,000 DDT
o It is non-dissolvable in water
**Beware of chemicals with Kow > 5
c. Weak organic acids and bases
▪ Many pesticides and drugs are weak organic acids and bases
2. Filtration (bulk flow) = diffuse through cell junctions
For example:
o Glomerulus pores ~70 nm
o Most cells ~4 nm
o Brain ~ 0 nm (blood-brain barrier)
3. Active transport = ATP-requiring transport against concentration gradient
o Important for excretion
o E.g. Multi-drug resistant proteins (MDRs)
▪ Cancer cells have MDRs – it detects lipophilic substances (drugs) that have
entered the cell and excrete them back out of the cell
▪ BBB also has MDR proteins
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
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