Lecture 2

Question 1

2 principles of toxicology

Answer 1

dose-response relationship

toxin has to interact with its molecular target in order to be toxic

Question 2

conc of oxygen/nitrogen in atmosphere

Answer 2

oxygen - 21%
nitrogen - 78%

Question 3

explain the dose-response concept

Answer 3

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

Question 4

what is the 1st principle of toxicology

Answer 4

the dose response concept

Question 5

“the total amount of material to which an organism is exposed”

Answer 5

dose

Question 6

“the amount of material penetrating into the organism through the route of exposure”

Answer 6

absorbed dose
(internal dose)

Question 7

define target organ dose and what is another name for it

Answer 7

amount of material received at the organ/tissue exhibiting a toxic effect

aka biologicall effevtive dose

Question 8

molecular target of carbon monoxide?
target ORGAN?

Answer 8

molecular - hemoglobin

target organ = vasculatre

Question 9

“received at”

Answer 9

target organ dose

Question 10

“penetrating into”

Answer 10

absorbed dose

Question 11

“total amount”

Answer 11

dose

Question 12

define median lethal dose (LD50)

Answer 12

dose that causes death in 50% of the animals tested

Question 13

define median effective dose (ED50)

Answer 13

dose that causes the desired effect in 50% of the animals tested

Question 14

define TI

Answer 14

therapeutic index - indication of drug safety

LD50/ED50

Question 15

true or false

high ED50 means high TI

Answer 15

FALSE

Question 16

do we want the TI to be high or low

Answer 16

HIGH

means the lethal dose is high and effective dose is smol

Question 17

margin of safety

Answer 17

LD1/ED99

Question 18

the 2nd principle of toxicology is the ___ ___ concept

Answer 18

molecular target

the chemical has to interact with its molecular target within the living organism

Question 19

what is the molecular target of SARS COV2

Answer 19

the spike protein ACE2 on human cells

Question 20

what is the pre requisite for adverse effects

Answer 20

exposure

Question 21

define exposure

Answer 21

the contact between a toxic agent and the living organism

Question 22

3 major routes of toxic agents exposure to the body

Answer 22

GI tract
lungs
skin

Question 23

acute vs subacute vs subchronic vs chronic exposure

Answer 23

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

Question 24

differentiate between elemental mercury (like in a thermometer) vs organic mercury (like in fish)

Answer 24

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

Question 25

most popular route of exposure

Answer 25

oral

Question 26

how many layers of barriers are there for oral ingestion (layers in GI)

Answer 26

3 epithelium, MALT (mucosa-associated lymphoid tissue), lumen

Question 27

3 mechanical tasks of the stomach

Answer 27

store, digest, empty

Question 28

name 2 factors that will alter gastric emptying time

Answer 28

food and pH changes

Question 29

the gas exchange that takes place in the alveoli is driven by what?

Answer 29

concentration gradient

Question 30

a particle size diameter of ___ and above will be removed by the upper respiratory tract

Answer 30

2 micrometers and greater

Question 31

issue with PM 2.5 micrometers

Answer 31

so small that it can get into the alveoli

Question 32

skin, lungs, and ingestion are the most common routes of exposure which is the quickest and why

Answer 32

inhalation only has 2 layers - epithelium type 1 and 2 and endothelial cells

Question 33

true or false the inhalation route of exposure has a large surface area

Answer 33

true

Question 34

approximate total surface area of the alveoli

Answer 34

100 square meters (1 tennis court)

Question 35

what is the quickest and most direct route of exposure

Answer 35

inhalation

Question 36

what weather increases absorption through the skin

Answer 36

hot weather

Question 37

which has a larger surface area - the skin or the alveoli

Answer 37

the alveoli!! (~100 square meters, only 1.5-2 square meters for skin)

Question 38

the skin tolerates ____ ---_____ times the exposure limit compared to ingestion or inhalation

Answer 38

100-1000

Question 39

true or false the skin is an excellent barrier (any exceptions)

Answer 39

true exceptions are acids, phenols, and lipophilic cimpounds like carbon tetrachloride