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tox > tox test 1 > Flashcards

tox test 1 Flashcards

1
Q

Toxicology

A

study of poisions

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2
Q

posion

A

a substance that can cause people or animals to die or to become very sick if it gets into their bodies especially by being swallowed.

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3
Q

both science and art

A

science-data gathering

art-predictive stage

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4
Q

classical period

A

classified plants by toxicity

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5
Q

Middle ages

A

pharmacopeias

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6
Q

Paracelsus

A

The dose makes the poison

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7
Q

Mathieu Orfila

A

father of modern toxicology

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8
Q

Toxicant exposure

A

model

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9
Q

Dose

A

an amount of a chemical

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10
Q

dosage

A

the amount per body weight (mg/kg/per day)

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11
Q

SAR structure-activity relationship

A

relationship between the structure and activity that gives indication to toxicity

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12
Q
  1. SAR
  2. testing in vitro
  3. animal bioassays
  4. human data and epidemiology
A

testing methods

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13
Q

ingestion
dermal
inhalation
injection

A

routes of exposure

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14
Q

vehicle

A

solvent that chemical is dissolved in

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15
Q

gauge

A

injected directly in the stomach

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16
Q

intraperitoneal

A

in stomach

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17
Q

intravenous

A

vein/blood

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18
Q

intramuscular

A

between muscles

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19
Q

subcutaneous

A

under skin

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20
Q

how much is necessary to produce toxicity?

A

response varies geometric not arithmetic increase

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21
Q

acute toxicity

A

single exposure for a few days weeks (14 days(

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22
Q

subacute toxicity

A

continous exposure over short period of time (14 days)

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23
Q

subchronic toxicity

A

continous exposure for a long period of time (90 days)

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24
Q

chronic toxicity

A

low doses for over a long period of time (more than 90 days)

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25
Q

LD50

A

lethal dose; dose at which 50% of the first test organisms die

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26
Q

Negative control

A

vehicle only used on test subject

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27
Q

dose response curve

A

s-shaped

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28
Q

probit

A

straight line

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29
Q

biological response

A

endpoint

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30
Q

Threshold dose/ NOEL

A

no effect or response found

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31
Q

synergism

A

increase in toxicity

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32
Q

antagonism

A

decrease in toxicity

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33
Q

risk assessment

A

the risk hazard is weighed against the benefits

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34
Q
  1. hazard identification
  2. dose-response evaluation
  3. exposure assessment
  4. risk characterization
A

Risk assessment 4 components

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35
Q

risk managemnets

A

decisions made concerning health risks

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36
Q
  1. exposure
  2. toxicokinetics
  3. toxicodynamics
A

3 phases of toxic action

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37
Q

ADME model

A

absorption, distribution,metabolism, excretion

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38
Q

Absorption

A

all chemical must cross at least one cell membrane to enter body.

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39
Q

lipophilicity

A

ability to cross phospholipid membranes

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40
Q

pH
charge
size
shape

A

absorption properties

41
Q

passive diffusion
facilitated diffusion
active transport
endo/exoytosis

A

cell entry methods

42
Q

oral, inhalation, dermal, injection

A

absorption routes

43
Q

topical, transdermal patches, sublingual,rectal

A

dermal

44
Q

oral

A

from mouth to large intestine (most absorbed in small intestine)

45
Q

Respiratory

A

from nose to alveoli

46
Q

Dermal

A

pass through epidermis to get to dermis (only highly permeable can pass and be effective)

47
Q

Half-life

A

half gets eliminated half stays in the body

48
Q

zero order

A

constant rate over time (straight line)

49
Q

first order

A

rapid at first than becomes slower

50
Q

-KC

A

constant at which proportion of drug loss per time unit

51
Q

clearance

A

volume of blood or plasma cleared of drug per time(dose divided by area under plasma concentration)

52
Q

bio availability

A

extent to which a drug or toxicant is absorbed orally compared with IV administration (AUCoral/DOSEoral divided by AUCiv/DOSEiv)

53
Q

Greater availability and absorption

A

as it gets closer to one but never one unless IV

54
Q

Biotransformation

A

chemical changes of parent chemical to metabolites

55
Q

Detoxification

A

metabolites become less toxic (best if molecule is hydrophilic, large, charged)

56
Q

intoxification/bioactivation

A

metabolites become more toxic

57
Q

Phase 1

A

parent is hydrolyzed, oxidized,or reduced

58
Q

Phase 2

A

conjugation (liver)

59
Q

Hydrolases

A

break bonds using water

60
Q
  • amidases
  • peptidases
  • cholinester hydrolases
  • carboxylester hydrolases
A

example of hydrolases

61
Q

serine hydrolases

A
  • family of enzymes

- catalytic site has amino acid serinewhich reacts with substrate

62
Q

catalytic triad

A

A set of three coordinated aminos that can be found in the active site of enzymes

63
Q

carboxylester Hydrolases (CES1 and 2)

A

-metabolize choline esters

64
Q

epoxide hydrolase

A
  • Acts on groups called epoxides and converts them to diols

- key metabolism of polycyclic aromatic hydrocarbons (coal, crude oil, and gasoline or when they are burned)

65
Q

Cytochrome P450

A
  • oxidation reactions
  • enzymes in SER(detoxifies) of cells
  • absorb at 450 nm(blue)
  • heme group binds to oxygen
66
Q

monooxygenases

A

add one oxygen in phase one

67
Q

Hydroxylation

A

add OH group

68
Q

Dealkylation

A

removal of alkyl group

69
Q

epoxidation

A

forming an epoxide

70
Q

hydrophobic molecules

A

beome more polar, conjugate, and get eliminated

71
Q

POPs

A

persistant oganic pesticides that never go away

72
Q

o-,s-,n- dealkylation

A

the removal of an alkyl group from O,S,N

73
Q

xenobiotic

A

foreign substances to the body (poisons)

74
Q

flavin containing monooxygenases

A

key to xenobiotic metabolism, contains FAD part

75
Q

Alcohol dehydrogenase (ADH)

A

-detoxification of alcohol (liver)

76
Q

conjugates

A

in phase 2 where metabolites become highly polar by combining to carbs, aminos, or small peptides(proteins). enzymes are located in cytosol

77
Q

Glucuronidation

A

conjugation with activated nucleoside diphosphate sugar uridine diphosphoglucuronic acid (UDPGA) sugar

78
Q

gluthathione conjugation

A

reacts with peroxides and other electrophilic compounds (ex. acetominophen)

79
Q

Acetylation

A

adds alkyl group

80
Q

N-Acetyltransferase (NATS)

A

xenobiotic metabolizing enzymes

81
Q

Active (catalytic) sites

A

found in enzymes it is where the reaction occurs

82
Q

Michaelis-Menten kinetics

A

Enzyme rate

83
Q

Allosteric sites

A

-sites where toxins can bind that are not active sites

84
Q

competitive inhibition

A

toxin binds at the active site E

85
Q

noncompetitive inhibition

A

toxin binds to another site on the E but substrate still can not go in active site

86
Q

Acetylcholinesterase

A

key enzyme in neuromuscular synapse (ex. sarin and VX deactivates neurons)

87
Q

receptors

A

proteins embedded in membranes or in cytoplasm which bind a signal molecule (ligand) (this is known as signal transduction system)

88
Q

agonists

A

toxicants which mimic the action of a natural neurotransmitter

89
Q

antagonists

A

toxin that binds to the receptor site but do not produce a response(signal)

90
Q

GABA Receptor

A

found in dendrites or dell body in postsynaptic membranes the ligand binds and opens Cl ion channels

91
Q

Tetrodotoxin (TTX)

A

found in pufferfish blocks sodium channel by binding-extracellular pore opening

92
Q

Lipid peroxidation

A

free radicals are formed on fatty acids also known as oxidative damage (damages cell membranes and organelles)

93
Q

mutagens

A

agents that cause mutations

94
Q

deamination agent

A

removal of amine group from adenine and cytosine

95
Q

alkylating agents

A

add alkyl groups to bases

96
Q

dimerization

A

adjacent thymines bond together

97
Q

Apoptosis

A

programmed cell death proteins known as capsases are “executioners”

98
Q

Necrosis

A

injury to cell that leads to death key factor is calcium regulation

99
Q

Cyclooxygenase (COX) inhibitors

A

enymes catalyze conversion of arachidonic acid to prostaglandin H2 (PGH2)

tox (4 decks)

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