Lecture 2 Flashcards
2 principles of toxicology
dose-response relationship
toxin has to interact with its molecular target in order to be toxic
conc of oxygen/nitrogen in atmosphere
oxygen - 21%
nitrogen - 78%
explain the dose-response concept
the magnitude of the toxic effect is a function of the concentration of the molecular targets that have been altered – which is related to concentration of the toxin at the site where the molecular targets are located
what is the 1st principle of toxicology
the dose response concept
“the total amount of material to which an organism is exposed”
dose
“the amount of material penetrating into the organism through the route of exposure”
absorbed dose
(internal dose)
define target organ dose and what is another name for it
amount of material received at the organ/tissue exhibiting a toxic effect
aka biologicall effevtive dose
molecular target of carbon monoxide?
target ORGAN?
molecular - hemoglobin
target organ = vasculatre
“received at”
target organ dose
“penetrating into”
absorbed dose
“total amount”
dose
define median lethal dose (LD50)
dose that causes death in 50% of the animals tested
define median effective dose (ED50)
dose that causes the desired effect in 50% of the animals tested
define TI
therapeutic index - indication of drug safety
LD50/ED50
true or false
high ED50 means high TI
FALSE
do we want the TI to be high or low
HIGH
means the lethal dose is high and effective dose is smol
margin of safety
LD1/ED99
the 2nd principle of toxicology is the ___ ___ concept
molecular target
the chemical has to interact with its molecular target within the living organism
what is the molecular target of SARS COV2
the spike protein ACE2 on human cells
what is the pre requisite for adverse effects
exposure
define exposure
the contact between a toxic agent and the living organism
3 major routes of toxic agents exposure to the body
GI tract
lungs
skin
acute vs subacute vs subchronic vs chronic exposure
acute - exposure for less than 24 hours
subacute - exposure for 1 day-1 month
subchronic - exposure from 1 month - 3 months
chronic - exposure for MORE THAN 3 MONTHS
differentiate between elemental mercury (like in a thermometer) vs organic mercury (like in fish)
organic mercury is more toxic. when elemental mercury gets into bodies of water it’s converted into METHYLMERCURY – if we eat or ingest via any route, it’s neurotoxic
most popular route of exposure
oral
how many layers of barriers are there for oral ingestion (layers in GI)
3
epithelium, MALT (mucosa-associated lymphoid tissue), lumen
3 mechanical tasks of the stomach
store, digest, empty
name 2 factors that will alter gastric emptying time
food and pH changes
the gas exchange that takes place in the alveoli is driven by what?
concentration gradient
a particle size diameter of ___ and above will be removed by the upper respiratory tract
2 micrometers and greater
issue with PM 2.5 micrometers
so small that it can get into the alveoli
skin, lungs, and ingestion are the most common routes of exposure
which is the quickest and why
inhalation
only has 2 layers - epithelium type 1 and 2 and endothelial cells
true or false
the inhalation route of exposure has a large surface area
true
approximate total surface area of the alveoli
100 square meters
(1 tennis court)
what is the quickest and most direct route of exposure
inhalation
what weather increases absorption through the skin
hot weather
which has a larger surface area - the skin or the alveoli
the alveoli!! (~100 square meters, only 1.5-2 square meters for skin)
the skin tolerates ____ —_____ times the exposure limit compared to ingestion or inhalation
100-1000
true or false
the skin is an excellent barrier
(any exceptions)
true
exceptions are acids, phenols, and lipophilic cimpounds like carbon tetrachloride
