Lecture 2 - Basic Principles of Toxicology

what does NOAEL stand for?

No Observed Adverse Effect Level

what is LD50 or LC50?

lethal dose/concentration that kills 50% of a test population

what is MTD?

minimum toxic dose

what is MLD/MLC?

minimum lethal dose/concentration

what value is likely of most clinical use?

Minimum Toxic dose?

What is included in the basic principle #1?

• therapeutic effect at certain level of dose, then if you increase dose you get toxic effect

• Toxicant = LD50 (mg/kg) - Rat (everything toxic at right dose)

• species specific values for toxicity (cats are not small dogs)

what is included in the basic principle #2?

• exposure does not equal intoxication

• toxicokinetics (ADME)

why does exposure not always equal intoxication?

• toxin must be absorbed and reach its site of action at a high enough concentration and for a sufficient period of time to cause a toxic effect (toxicokinetics)

• why treatment often involves decontamination

what are the three important aspects of basic toxicokinetics?

• similar to basic pharmacokinetics

• big species differences

• Basic Events: ADME (absorption, distribution, metabolism, excretion)

what is absorption?

• how it gets into the body (oral/ingestion, dermal exposure, injection (IV, SQ, IM, IP), inhalation)

can you minimize absorption?

Yes, by using decontamination methods such as activated charcoal, washing skin, or avoiding exposure routes.

what is distribution?

where it goes through the body (fat solubility vs water solubility, protein building, pH of tissues and compartments)

what is metabolism?

• what happens to it when it gets there (biotransformation)

• take problem molecule and break it down into baby molecules that are no longer problem

• often converted to a more water-soluble product

what is excretion?

• how does it get out of the body

what are the primary routes of excretion?

• urinary

• biliary/fecal

• milk, sweat, saliva (more secondary routes)

how does the typical dose/response curve work?

at low concentrations there is little to no response, but at concentration increases, so does the response

what are the exceptions about the dose/response curve?

Essential nutrients dont follow the dose/response curve, they have more of a region of homeostasis

what is the therapeutic index?

ratio of the dose of the drug that produces an unwanted (toxic) effect to that producing a wanted (therapeutic) effect (LD50/ED50)

what is the safety ratio?

LD1/ED99

what is the idea when it comes to the therapeutic index?

ideally you want a wider (larger) therapeutic index

what is included in basic principle #3?

• dose/response curve

• region of homeostasis

• therapeutic medications

• therapeutic index

what is involved in basic principles #4?

many factors influence toxicity

• characteristics of animal/animals exposed

• route of exposure

• frequency of exposure

• characteristics of the toxicant

• Environmental conditions