Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Toxicology UNC Fall 2023 > E2L3 Dose-Response > Flashcards

E2L3 Dose-Response Flashcards

1
Q

what did Paracelsus say?

A

everything is toxic; its the dose that separates something from being therapeutic or toxic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what is exposure?

A

contact with a toxicant by an organism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what does the exposure depend on?

A

vectors and the exposure pattern

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what are vectors?

A

how the toxicant comes into contact with the organism; water, air, soil, food, etc.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what is the exposure pattern?

A

intensity, frequency, and duration of exposure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what is acute exposure?

A

usually refers to a single exposure that is less than 24 hours (rapid)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what is a subacute exposure?

A

repeated/continuous exposure for less than or equal to 1 month

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what is subchronic exposure?

A

repeated/continuous exposure for 1-3 months (less than 10% of life span)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what is chronic exposure?

A

repeated/continuous exposure for more than 3 months (more than 10% of life span)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

why do effects after repeated exposures sometimes differ from those after acute exposure?

A
  • acute and chronic exposure may have different mechanisms
  • repair mechanisms may be working for acute exposure, but sometimes wear down after chronic exposure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what is the magnitude of the response related to?

A

the concentration at the target site is typically related (proportional) to exposure dose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what is a quantal response?

A

all-or-none response; often used in population studies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what do quantal responses often resemble?

A

Gaussian distribution

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what is a graded response?

A

continuum; often measured in individuals (ex: ability of drug to increase BP or HR)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what is ED50?

A

the dose that corresponds to 50% maximal response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what is potency in terms of measurement?

A

how far to the left or right on the dose-response curve does the curve lie? (more left = more potent)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what is a measurement of potency?

A

ED50/EC50

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what is a measure of efficacy?

A

maximal response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what is efficacy?

A

the greater the maximal effect, the more efficacious the drug is (the more toxic)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

when is EC50 a useful measure of potency?

A

only if the curves are parallel to each other; when the slopes are different, then its not a very useful measure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what is a common assumption made with risk (and especially with a lot of cancer-causing chemicals)?

A

the dose-response relationship is not only linear, but there is no threshold! (assumption that it goes through 0)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what is threshold?

A

the largest dose below which there is no response (or probability of an individual responding essentially zero)

23
Q

when are thresholds well established?

A

in acute responses (more difficult to define in chronic responses)

24
Q

what can influence dose-response relationship variability?

A
  • a toxicant can cause various effects, each with its own dose-response relationship and mechanisms
  • different types of exposure (acute vs. chronic for example) and route of exposure can result in different dose-response relationships (for the same toxicant)
25
what genetic and environmental factors have the ability to influence dose-response?
- life stage (age) - species/strain - sex - absorption/distribution - metabolism - immunologic reactions - tissue reserve capacity - coexisting disease - inflammation - coexposures - nutritional status - obesity - pregnancy
26
what is an example of a species difference genetic factor influencing dose-response?
while looking at activity of a drug metabolizing enzyme in hepatocytes taken from either a rat or a human, research showed that there was a difference in maximal response (efficacy); the rat was more potent
27
what is an example of environmental factors influencing dose-response?
acetaminophen in the presence of LPS caused rats to become much more sensitive to hepatotoxicity to acetaminophen in the presence of LPS (curve shifted left)
28
what is the margin of safety?
the dose associated with toxicity in 1% of animals over the dose that is efficacious in 99% of the animals
29
what is the equation for margin of safety (MOS)?
TD1/ED99
30
when is therapeutic index used most often?
in drug development
31
what is the equation for therapeutic index?
TD50/ED50 (dose associated with toxicity of 50% of animals over dose associated with response of 50% of animals)
32
what are the four components of risk assessment?
1. Hazard identification/characterization 2. Dose-response assessment 3. Exposure assessment 4. Risk characterization
33
what is LOAEL (lowest observed adverse effect level)?
the lowest dose/data point where we have a significant difference in control
34
what is NOAEL (no observed adverse effect level)?
the highest dose at which there is no significant increase in some toxicity measure
35
what is the POD (point of departure)?
the dose that produces a response that is a predetermined departure from the control response
36
what is the BMD (benchmark dose)?
the dose that corresponds to a pre-determined level of response (ex: BMD10 = dose that corresponds to a 10% increase in response relative to baseline)
37
why use BMD instead of NOAEL or LOAEL?
when we use BMD, we're using the whole curve, so it provides info about risk at doses near the BMD as well as provides consistency in calculating safe doses
38
what are the two approaches to risk assessment?
1. "safety factor" approach 2. "acceptable risk" approach
39
what is the "safety factor" approach to risk assessment used for?
nongenotoxic endpoints (most of what we study)
40
what is the goal of the "safety factor" approach to risk assessment?
to estimate an exposure dose (known as the reference dose AKA "RfD") that will be safe/nontoxic
41
what is the reference dose (RfD)?
an estimate of a daily exposure (mg/kg/day) to humans (including sensitive individuals) that is likely to be without appreciable risk of adverse effects over a lifetime
42
what is the approach of the "safety factor" approach for risk assessment?
use NOAEL or BMD as an estimate of minimal toxic effect, then divide by a "safety factor" to arrive at an acceptable exposure dose
43
what is the equation for the reference dose (RfD)?
RfD = NOAEL/(10[human--> human extrapol.] X 10[for human sensitivity]) = NOAEL/100
44
what is the "acceptable risk" approach of risk assessment used for?
genotoxic (cancer) endpoints
45
what is the goal of the "acceptable risk" approach of risk assessment?
to estimate an exposure dose that will result in a very small, acceptable risk of developing cancer
46
what is the assumption of the "acceptable risk" approach of risk assessment?
responses to carcinogens have a linear relationship to dose, and there is NO threshold; exposure to even small doses of carcinogens will increase the probability of developing cancer
47
what is the approach of the "acceptable risk" approach of risk assessment?
- establish an increased cancer risk that is "acceptable" in people - perform "carcinogenicity bioassay" in animals, in which large doses (ex. 3) of carcinogen are used that cause cancers above the spontaneous rate - extrapolate results (tumor incidence) to small exposure doses to estimate an acceptable risk, assuming no threshold
48
what are the disadvantages of the "acceptable risk" approach of risk assessment?
- we don't know what the dose-response curve really looks like - assumption that there is no threshold - assumption that tiny doses of radiation have a possibility of causing tumors
49
what does a monotonic dose-response relationship mean?
give a dose --> get a response linear relationship between dose and response
50
what is an example of a non-monotonic dose-response relationship?
iron: - we need a certain level of iron for hemoglobin to carry oxygen - if we have too little, we experience a toxic effect (anemia) - if we have too much, we also experience a toxic effect (oxidative stress, GI tract injury, etc.)
51
what is hormesis?
beneficial response at low dose, toxic effect at high dose
52
what is an example of hormesis?
arsenite and lymphocyte proliferation: - at low doses of arsenite, we see an increase in the mitogenic effect - at higher doses, we see a decrease in proliferation
53
what can oxidative stress cause?
the activation of stress responses, such as the TF "NERF2"
54
what does NERF2 do?
it increases the amount and activity of antioxidant enzymes like glutathione peroxidase which is then protective (so maybe a little stress is good)

Toxicology UNC Fall 2023 (3 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions