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DABT Exam 2024 > Principles Of Toxicology (Chapter 2 EOT) > Flashcards

Principles Of Toxicology (Chapter 2 EOT) Flashcards

1
Q

The study of adverse effects of chemical, biological, or physical agents on living organisms and the environment

A

Toxicology

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2
Q

Foreign or synthetic substances with different intended purposes that are harmful are called ? or ?.

A

Xenobiotics or toxicants

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3
Q

Naturally occurring harmful substances that originate from plants, microbial organisms, or venoms are called ?

A

Toxins

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4
Q

Dose of chemicals needed to produce death in 50% of treated animals

A

LD50

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5
Q

Limitations of using the LD50 include:

A

Doesn’t reflect full spectrum of toxicity (carcinogens, teratogens, neurobehavior effects); doesn’t take into account individual variability which makes increases susceptibility to a toxin

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6
Q

Type of toxicologist that identifies cellular, biochemical, and molecular mechanisms by which chemicals exert toxic effects on living organisms

A

Mechanistic toxicologist

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7
Q

Hypersensitivity or allergic reactions require what in order to occur?

A

Prior exposure to the same or structurally similar chemical

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8
Q

The abnormal reactivity of an individual to a chemical based on their genetics or other individual sensitivity factors

A

Chemical idiosyncrasy

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9
Q

Idiosyncratic Drug reactions involve a combination of individual differences in the ability to:

A

1)form a reactive intermediate usually through oxidation to an electrophilic intermediate
2) detoxify the reactive intermediate through hydrolysis or conjugation
3) mount an immune response through human leukocyte antigens (HLAs) and T cells
4) cause cell death

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10
Q

What factors beyond genetics can cause idiosyncratic reactions?

A

Inflammatory stress, infection, mitochondrial dysfunction, environmental factors

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11
Q

What organ systems are most likely to be affected by idiosyncratic reactions?

A

Skin, Liver, hematopoietic and immune systems

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12
Q

The likelihood of a toxic response to be reversed largely depends on ?

A

The ability of the injured tissue to adapt, repair and regenerate

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13
Q

The target organ of toxicity and the site of the highest concentration of the exposed chemical are almost always the same.

A

False

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14
Q

This type of effect occurs when the combined responses of two chemicals are equal to the sum of the responses to each chemical given alone

A

Additive effect (2+3=5)

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15
Q

Type of effect when the combined responses of two chemicals are much greater than the sum of the response to each chemical when given alone

A

Synergistic effect (2+2=20)

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16
Q

Occurs when one substance does not produce any toxicity on a particular tissue or system, but when added to another chemical makes that chemical much more toxic

A

Potentiation (0 + 2 =10)

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17
Q

Occurs when two chemicals administered together interfere with each other’s actions or one interferes with the action of another

A

Antagonism (4+6= 8), (4+ (-4)= 0), (4+0=1)

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18
Q

Four types of antagonism are:

A

Receptor, chemical, dispositional, functional

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19
Q

Receptor antagonists are also known as

A

Blockers

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20
Q

Chemical antagonism is also known as

A

Inactivation

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21
Q

Chelation of metal ions is an example of what kind of antagonism

A

Chemical

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22
Q

Type of antagonism when the absorption, distribution, biotransformation, or excretion of a chemical is altered so the concentration or duration of chemical at target organ is reduced

A

Dispositional

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23
Q

Type of antagonism when 2 chemicals counterbalance each other by producing opposing effects on the same physiological function often by using different signaling pathways

A

Functional antagonism

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24
Q

This type of tolerance results from a lower availability of receptors and/or mediators (neurotransmitters)

A

Chemical or cellular tolerance

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25
Q

Type of tolerance when the amount of the chemical reaching the target organ decreases over time

A

Dispositional tolerance

26
Q

Chemicals with higher LD50 values are more/less fatal than those with lower LD50 values

A

Less fatal

27
Q

VX nerve gas has an LD50 that is 5x higher/lower than botulinum toxin

A

True: VX nerve gas 1 mg/kg, botulinum toxin .00001 mg/kg

28
Q

A chemical given by inhalation would be more or less effective if given orally

A

Less
Order of effectiveness is: IV, inhalation, IP, SQ, IM, PO, topical

29
Q

Acute exposure is defined as less than how many hours

A

24

30
Q

Acute exposure by inhalation is usually for how many hours

A

4 but can be up to 24

31
Q

Subacute exposure is repeated exposure for up to how many months

A

1 month or less

32
Q

Subchronic exposure is repeated exposure for how many months

A

1 to 3 months

33
Q

Chronic exposure is repeated exposure for how many months

A

More than 3; usually refers to a year of dosing

34
Q

The minimal effective dose of any chemical that evokes a stated all or none response is a

A

Threshold dose

35
Q

Quantal dose- response relationship curves usually follow what type of distribution

A

Normal or Gaussian distribution curves

36
Q

The linear portion of a sigmoid curve represents what

A

The limits of one standard deviation of the mean and median in a normal distribution population

37
Q

The mean +/- one, two and three SD’s in a normal distribution is equivalent to what percent of the population

A

68.3%, 95.5%, 99.7% respectively

38
Q

What is an NED and how is it obtained

A

Normal equivalent deviation, calculated by using % response to derive units of deviation from the mean when using a normal distribution curve

39
Q

An 80% response would give what NED

A

+/- 1

40
Q

What is a probit unit

A

Converted NEDs by adding 5 to the value; used to avoid negative numbers; short form of probability unit

41
Q

An NED of -2 would equate to what in probit units

A

3

(-2 + 5)

42
Q

A probit transformation would adjust a normal distribution of quantal data to what

A

A straight line

43
Q

How is the ED50 obtained from a probit unit diagram

A

Drawing a horizontal line at the probit unit 5 mark through the dose effect line. The intersection is the ED50 on the abscissa

44
Q

Field of study that examines the relationship between body weight and various other physiological parameters (basal metabolic rate, heart rate, blood flow)

A

Allometry

45
Q

What formula is used in allometrix studies

A

Y= a W^b

Y is biological parameter of interest
A and b are constants that relate Y to body weight

46
Q

Formula for comparing body weight to body surface area

A

SA=10.5 x (body weight in g)^0.67

47
Q

How do you calculate the human equivalent dose

A

HED= animal dose in mg/kg x (animal weight in kg/human weight in kg)

48
Q

What is PBPK modeling

A

Physiologically based pharmacokinetic modeling; a type of computer modeling that is used to scale doses across species

49
Q

What is a monotonic response?

A

Increasing dose will cause a steady unidirectional change in response; can be uphill or downhill curves

50
Q

Type of dose-response curve when multiple inflection points exist along a curve that changes shape

A

Nonmonotonic

51
Q

U, J, or inverted U shaped curves are examples of what types of dose-responses

A

Nonmonotonic

52
Q

Hormetic effects or hormesis occurs when chemicals exhibit what kind of effect at low exposures but opposite kinds of effects at high doses

A

Beneficial at low; harmful at high

53
Q

Type of model where it’s assumed there is a direct and proportional relationship between dose and response even at very low doses

A

Linear, nonthreshold

54
Q

Dose at which toxicity is first observed

A

Threshold

55
Q

Concept that there are levels of exposure for chemicals below which the risk to human health is not appreciable

A

Threshold of toxicologic concern (TTC)

56
Q

Essential nutrients for organisms frequently fall under what type of graded dose-response curve

A

U shaped (linear, nonmonotonic)

57
Q

An example of hormesis is

A

Alcohol consumption reducing risks of coronary artery disease at low consumption but increasing risks of cancer at high consumption

58
Q

The nonmonotonic dose-response curves observed with endocrine disruptors can be explained by what mechanisms

A

Dose-dependent cytotoxicity, cell and tissue specific receptors and cofactors, receptor selectivity and down-regulation, receptor competition, endocrine negative feedback loops

59
Q

The ratio of the dose required to cause a toxic effect to the dose required produce the desired therapeutic response

A

Therapeutic index; TD59/ED50

60
Q

How is margin of safety calculated?

A

MOS= TD1/ED99

61
Q

How is chronicity index calculated? What is ideal value? What are the units?

A

One dose TD50 (mg/kg) /90 dose TD50 (mg/kg/day); ideal is 1; no units

DABT Exam 2024 (2 decks)

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