Toxicology Basics - Intro & Toxicokinetics Flashcards
therapeutic index equation
TI = LD50 / ED50
standard safety margin equation
SSM = LD1 / ED99
acute toxicant exposure vs chronic toxicant exposure
acute: exposure to single or multiple doses over 24 hrs
chronic: exposure for 3 months or longer
alternative name for a poison
toxicant
poison that originates from biological processes “biotoxin”
toxin
quantity or amount of poison that causes a toxic effect
toxicity
disease state that results from exposure to a poison
toxicosis
amount of toxicant received per animal
dose
amount of toxicant per unit animal mass or weight; time can also be included as a metric
dosage
how the animal is exposed to the toxicant; oral, feed, drink, dermal, inhalation, etc.
route of exposure
highest dose of a toxicant where no toxic effects are observed
threshold dose
acute dose resulting in death; usually presented as the dose resulting in death of 50% of animals (LD50); can also be expressed as dose resulting in death of 10% of animals (LD10)
lethal dose
lowest concentration of a chemical in a matrix (usually feed or water) that causes death; commonly used for lethality for fish or wildlife species
lethal concentration
dose of a drug or toxicant that produces some desired effect in 50% of the population
effective dose
bioavailability equation
B = AUCRoute X x DoseIV
AUCIV x DoseRoute X
What factors affect the passage of toxicants across biological membranes?
concentration gradient across the membrane
surface area of the membrane
toxicant permeability
macromolecule binding
factors of small intestinal absorption
largest barrier to intestinal absorption is permeability – factors include solubility, metabolism, transporters and transit time
factors of dermal absorption of toxicants
can a water-soluble toxicant be expected to cross the skin
surface area & perfusion
lipophilic and hydrophilic
YES
What is the difference between diffusion- and perfusion-limited drug distributions?
Diffusion limited: based on easiness of diffusion/how quick it can get across; weak acids/bases easiest to in/out of tissues
Perfusion limited: based on blood flow to certain organs, brain/liver/intestines/kidney will be affect the fastest due to amount of blood flow they receive
Does metabolism always involve the disappearance of a toxicant? What other role can metabolism play in toxicant exposure?
no, in general metabolism is detoxifying but metabolic activation is sometimes required for toxic effect
metabolites can be active, toxic, inactive, nontoxic
how are toxicants eliminated from the body? main ones?
urine ** renal
feces ** hepatic
sweat
saliva
milk
exhalation
factors of renal elimination and factors of GFR
filtration, active secretion, reabsorption
blood flow
protein binding
factors of hepatic elimination
blood flow
protein binding
enzymatic acitivty
Be able to describe how the terminal half-life of a toxicant can influence the treatment of a poisoned animal.
important indicator of treatment duration or residue time
