Principles of toxicology

Question 1

define toxin

Answer 1

substance produced by a living organism that causes an adverse reaction

Question 2

define poison

Answer 2

substance that disturbs the structure or function of an organism

Question 3

LD50

Answer 3

dose that produces death in 50% of pop

Question 4

LC50

Answer 4

concentration that is lethal in 50% of pop

Question 5

TD50

Answer 5

dose that produces define toxicity in 50% of pop

Question 6

NOAEL

Answer 6

no obs. adverse effects level - max dose with no bad effects

Question 7

LOAEL

Answer 7

lowest observed adverse effects level - first dose you see an effect

Question 8

3 steps to risk assessment in toxins

Answer 8

1. identify hazards
2. assess exposure
3. examine dose-response relationship

Question 9

3 types of toxicology data

Answer 9

1. structure activity analysis
2. in vitro tests - cell, or organ level
3. in vivo - animal or human studies

Question 10

4 duration levels of tests

Answer 10

acute, subacute, subchronic, chronic

Question 11

3 types of human studies

Answer 11

1. case reports/series
2. epi studies
3. clinical trials

Question 12

3 mechanisms of toxicity

Answer 12

1. reversible binding of parent to receptor
2. reversible binding of metabolite to receptor
3. bioactivation of non-toxic to toxic meatbolite that irreversibly bind or oxidizes

Question 13

4 implications of receptor mediated toxicity

Answer 13

1. should be reversible
2. should be dose related
3. should be tissue specific
4. all compounds that bind to same receptor should have similar effects

Question 14

what is indirect vs. direct exposure assessment

Answer 14

direct - look in blood

indirect - look at air (eg) and then extrapolate

Question 15

what is biomagnification

Answer 15

toxins adding up the food chain

Question 16

what are 2 types of dose response assessments

Answer 16

graded and quantal

Question 17

what is graded assessment

Answer 17

y axis is continuous and represents that response in effect

Question 18

what is quantal assessment

Answer 18

y axis represents number of population that had a specific defined response

Question 19

3 assumptions of the dose response relationship

Answer 19

1. response was due to the drug administered
2. degree of response is related to the magnitude of the repsonse
3. response is well defines and quantifiable

Question 20

what is hormesis

Answer 20

concept that too little of a substance or too much can be bad and optimal dose is in the middle

Question 21

potential factors influencing toxicity

Answer 21

1. dose/duration
2. route
3. age
4. sex
5. diet (worse if malnourished)
6. disease
7. genetics
8. env . modifiers

Question 22

5 processes that affect toxicity

Answer 22

1. elimination
2. bioactivation
3. detoxification of reactive intermediates
4. cytoprotective pathways
5. repair of damaged cell macromolcules

Question 23

what is the therapeutic index

Answer 23

compares does that is effective to dose that is toxic (LD50/ED50) - want it to be high (TILE)

Question 24

what is certain safety factor

Answer 24

CSF = LD1/ED99

Question 25

what is the reference dose

Answer 25

estimate of daily exposure that is assumed to be without any negative impact

Question 26

how is RfD calculated

Answer 26

NOAEL withmadigying safety factors taken into account

RfD = NOAEL/ (safety factor x modifying factor)

Question 27

what is benchmark dose method

Answer 27

dose that produces a defined outcome (like headache) using the lowest confidence interval

Question 28

what is usually accepted margin of safety

Answer 28

100

Question 29

how do we calculate is have hit margin of safety of dose

Answer 29

TD10/exposure