tox test 1 Flashcards
1
Q
Toxicology
A
study of poisions
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.
3
Q
both science and art
A
science-data gathering
art-predictive stage
4
Q
classical period
A
classified plants by toxicity
5
Q
Middle ages
A
pharmacopeias
6
Q
Paracelsus
A
The dose makes the poison
7
Q
Mathieu Orfila
A
father of modern toxicology
8
Q
Toxicant exposure
A
model
9
Q
Dose
A
an amount of a chemical
10
Q
dosage
A
the amount per body weight (mg/kg/per day)
11
Q
SAR structure-activity relationship
A
relationship between the structure and activity that gives indication to toxicity
12
Q
- SAR
- testing in vitro
- animal bioassays
- human data and epidemiology
A
testing methods
13
Q
ingestion
dermal
inhalation
injection
A
routes of exposure
14
Q
vehicle
A
solvent that chemical is dissolved in
15
Q
gauge
A
injected directly in the stomach
16
Q
intraperitoneal
A
in stomach
17
Q
intravenous
A
vein/blood
18
Q
intramuscular
A
between muscles
19
Q
subcutaneous
A
under skin
20
Q
how much is necessary to produce toxicity?
A
response varies geometric not arithmetic increase
21
Q
acute toxicity
A
single exposure for a few days weeks (14 days(
22
Q
subacute toxicity
A
continous exposure over short period of time (14 days)
23
Q
subchronic toxicity
A
continous exposure for a long period of time (90 days)
24
Q
chronic toxicity
A
low doses for over a long period of time (more than 90 days)
25
LD50
lethal dose; dose at which 50% of the first test organisms die
26
Negative control
vehicle only used on test subject
27
dose response curve
s-shaped
28
probit
straight line
29
biological response
endpoint
30
Threshold dose/ NOEL
no effect or response found
31
synergism
increase in toxicity
32
antagonism
decrease in toxicity
33
risk assessment
the risk hazard is weighed against the benefits
34
1. hazard identification
2. dose-response evaluation
3. exposure assessment
4. risk characterization
Risk assessment 4 components
35
risk managemnets
decisions made concerning health risks
36
1. exposure
2. toxicokinetics
3. toxicodynamics
3 phases of toxic action
37
ADME model
absorption, distribution,metabolism, excretion
38
Absorption
all chemical must cross at least one cell membrane to enter body.
39
lipophilicity
ability to cross phospholipid membranes
40
pH
charge
size
shape
absorption properties
41
passive diffusion
facilitated diffusion
active transport
endo/exoytosis
cell entry methods
42
oral, inhalation, dermal, injection
absorption routes
43
topical, transdermal patches, sublingual,rectal
dermal
44
oral
from mouth to large intestine (most absorbed in small intestine)
45
Respiratory
from nose to alveoli
46
Dermal
pass through epidermis to get to dermis (only highly permeable can pass and be effective)
47
Half-life
half gets eliminated half stays in the body
48
zero order
constant rate over time (straight line)
49
first order
rapid at first than becomes slower
50
-KC
constant at which proportion of drug loss per time unit
51
clearance
volume of blood or plasma cleared of drug per time(dose divided by area under plasma concentration)
52
bio availability
extent to which a drug or toxicant is absorbed orally compared with IV administration (AUCoral/DOSEoral divided by AUCiv/DOSEiv)
53
Greater availability and absorption
as it gets closer to one but never one unless IV
54
Biotransformation
chemical changes of parent chemical to metabolites
55
Detoxification
metabolites become less toxic (best if molecule is hydrophilic, large, charged)
56
intoxification/bioactivation
metabolites become more toxic
57
Phase 1
parent is hydrolyzed, oxidized,or reduced
58
Phase 2
conjugation (liver)
59
Hydrolases
break bonds using water
60
- amidases
- peptidases
- cholinester hydrolases
- carboxylester hydrolases
example of hydrolases
61
serine hydrolases
- family of enzymes
| - catalytic site has amino acid serinewhich reacts with substrate
62
catalytic triad
A set of three coordinated aminos that can be found in the active site of enzymes
63
carboxylester Hydrolases (CES1 and 2)
-metabolize choline esters
64
epoxide hydrolase
- 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
Cytochrome P450
- oxidation reactions
- enzymes in SER(detoxifies) of cells
- absorb at 450 nm(blue)
- heme group binds to oxygen
66
monooxygenases
add one oxygen in phase one
67
Hydroxylation
add OH group
68
Dealkylation
removal of alkyl group
69
epoxidation
forming an epoxide
70
hydrophobic molecules
beome more polar, conjugate, and get eliminated
71
POPs
persistant oganic pesticides that never go away
72
o-,s-,n- dealkylation
the removal of an alkyl group from O,S,N
73
xenobiotic
foreign substances to the body (poisons)
74
flavin containing monooxygenases
key to xenobiotic metabolism, contains FAD part
75
Alcohol dehydrogenase (ADH)
-detoxification of alcohol (liver)
76
conjugates
in phase 2 where metabolites become highly polar by combining to carbs, aminos, or small peptides(proteins). enzymes are located in cytosol
77
Glucuronidation
conjugation with activated nucleoside diphosphate sugar uridine diphosphoglucuronic acid (UDPGA) sugar
78
gluthathione conjugation
reacts with peroxides and other electrophilic compounds (ex. acetominophen)
79
Acetylation
adds alkyl group
80
N-Acetyltransferase (NATS)
xenobiotic metabolizing enzymes
81
Active (catalytic) sites
found in enzymes it is where the reaction occurs
82
Michaelis-Menten kinetics
Enzyme rate
83
Allosteric sites
-sites where toxins can bind that are not active sites
84
competitive inhibition
toxin binds at the active site E
85
noncompetitive inhibition
toxin binds to another site on the E but substrate still can not go in active site
86
Acetylcholinesterase
key enzyme in neuromuscular synapse (ex. sarin and VX deactivates neurons)
87
receptors
proteins embedded in membranes or in cytoplasm which bind a signal molecule (ligand) (this is known as signal transduction system)
88
agonists
toxicants which mimic the action of a natural neurotransmitter
89
antagonists
toxin that binds to the receptor site but do not produce a response(signal)
90
GABA Receptor
found in dendrites or dell body in postsynaptic membranes the ligand binds and opens Cl ion channels
91
Tetrodotoxin (TTX)
found in pufferfish blocks sodium channel by binding-extracellular pore opening
92
Lipid peroxidation
free radicals are formed on fatty acids also known as oxidative damage (damages cell membranes and organelles)
93
mutagens
agents that cause mutations
94
deamination agent
removal of amine group from adenine and cytosine
95
alkylating agents
add alkyl groups to bases
96
dimerization
adjacent thymines bond together
97
Apoptosis
programmed cell death proteins known as capsases are "executioners"
98
Necrosis
injury to cell that leads to death key factor is calcium regulation
99
Cyclooxygenase (COX) inhibitors
enymes catalyze conversion of arachidonic acid to prostaglandin H2 (PGH2)
