Chemical tox Flashcards
(116 cards)
1
Q
Which of the following would you consider not to be a xenobiotic compound to humans? Penicillin lysergic acid ochratoxin A lactic acid
A
lactic acid (body makes it naturally
2
Q
Define toxicity
A
acute death, cancer, teratogenicity, allergic reactions
3
Q
to say that a substance is non -toxic means that:
A
it would require a large dose to cause toxic effects
4
Q
Comparing the toxicity of a toxicants in rats vs humans could be considered to be an example of: comparative toxicology epidemiology Bradford-hill criteria inter-species extrapolation toxicity towards a non-target organism
A
toxicity towards a non-target organism
5
Q
According to IRAC, ochratoxin A is classified as what type of carcinogen?
A
Group 2B
6
Q
Which compounds give a J-shaped hormetic dose-response relationship
A
Ethanol
7
Q
Which dose-response relationship is used to characterize carcinogens?
A
linear dose
8
Q
According to Environment Canada a compound with a logKow greater then ? is likely to bioaccumulate
A
3.7
9
Q
Which compound has the lowest logKOW value pyrene naphthalene dichlorobenzene phenol benzene
A
phenol
10
Q
Which compound has the highest logKOW value benzene hexachlorobenezene pyrene benzo[a]pyrene phenanthrene
A
benzo[a]pyrene
11
Q
which compound I snot a surfactant sodium dodecylsulfate soap prostanoic acid bile salts octanol
A
octanol
12
Q
What type of surfactant aggregate is produced in non polar solvents
A
reverse micelles
13
Q
for a substance wit chemical structure phCH2CH2CO2H, th epic is likely to be close to
A
5
14
Q
for cocane, a base whose pka is 8.6, water solubility is likely to be highest at pH
A
3.5 so its protonates
15
Q
cocane, whose pjs is 8.6 is likely to be absorbed from the GI tract in the
A
small intestine
16
Q
pjs of anthracine is likely to be close to
A
none of the above
17
Q
anthracine is likely to be absorbed from the GI tract in the
A
(anywhere)
18
Q
from the list below choose the stringiest nucleophile in water OH NH3 F- HS- phenoxide
A
hs
19
Q
From the list below choose the stringiest nucleophile in DMSO water phenol HS OH
A
oh
20
Q
which solvent I snot classified as polar protic
A
DMF
21
Q
What does metabolism allow
A
the enzymatic conversion of chemicals to more polar compounds
22
Q
primary site of xenobiotic metabolism
A
liver
23
Q
CYP450 derives its name from optical properties of
A
Fe(II)-Cyp450-CO
24
Q
define polar protic
A
polar protic solvent are capable of hydrogen bonding because they contain at least one hydrogen atom attached to one electronegative atom
25
what makes a polar functional group
if its hydrophilic (water loving), its polar
26
examples of polar fictional groups
OH, NH2, Co2H
27
where are polar substances NOT taken up
the gut (does not break the barrier)
28
what makes a functional group non-polar
hydrophobic/lipophilic substance (most likely a hydrocarbon functional group)
29
What three atoms can be added to molecules to make them more lipophilic
BR, CL, I
30
What effect does Cl, BR, and I have on a molecule
- increases lipophilicity
| - increases London forces
31
describe solubility with polar/nonpolar
like dissolves like (polar W polar, Nonpolar W non polar)
32
what is the equation for partition constant
k= ([ solute in solvent 2])/([] soute in souvent 1])
33
What are the consequences of having his lipophilictty
1) uptake into fatty tissues
| 2) bioaccumulation (>3.7)
34
equation for relationship between KOW and bioconcentration factor
Bcf= [toxicant in aquatic organism]/[toxicant in surrounding water]
35
name 6 aromatic compounds
benzen, naphalene, anythracenbe, phenaline, pyrene, benzo[a]pyrene],[benzo[2]pyrene
36
what is an aromatic compound
contain conjugated planar ring systems
37
what does surfactant stand for
surface active agent
38
describe the formation os micelles in polar solvent
anything with the hydrophobic tails pointed in
39
describe the formation of micelles in non polar solvent
anything with hydrophobic tails pointed out
40
what is a prostaglandin
a family of compounds that have the 20-carbon skeleton of prostanoic acid
41
how are prostaglandins made in the body
synthesized from membrane-bound 20-carbon polyunsaturated fatty acids in response to specific body triggers
42
name a biological surfactant
bile salt
43
what do bile salts fo
act as a surfactant
| emulsify lipids
44
describe heterolytic bond cleavage
only one of the atoms gets the electrons, the other one gets nothing
45
describe hemolytic bond cleavage
both of the atoms get an electron
46
name the three hydrogen halides
Hal
Hbr
HI
47
name the tree oxides
H2SO4
HNO3
HCLO4
48
main acid/base property of xenobiotics
the uncharged form of the acid or base is more lipophilic (and more easily taken up in the GI tract)
49
describe acid/base properties of carboxylic acids and phenols
acidic conjugate is uncharged, basic conjugate is ionic
50
describe acid/base properties of nitrogen bases
acidic conjugate is ionic, basic conjugate is uncharged
51
what is a nucleophile
an electron-rich molecule that has at least one pair of unshared electrons
52
what charge do nucleophiles usually have
negative
53
what are the four factors that contribute to nucleophilicity
charge
electronegativity
solvet
steric hindrance
54
describe how charge effects nucleophilicity
- the conjugate base of a neutral species is always a better nucleophile
- nucleophilicity increases with electron density
55
describe how electronegativity effects nucleophilicity
nucleophilicity increases with decreased electronegativity
| th less electronegative an atom, the less tightly-held the electrons will be
56
describe how the solvent effects nucleophilicity
nucleophilicity increases going down the periodic table
57
describe how steric hindrance effects nucleophilicity
bulkiness/shape/greasiness
58
Describe the bonding between polar solvent and nucleophiles
a polar solvent can participate in hydrogen bonding with a nucleophile, creating a shell of solvent molecules. This makes the nucleophiles less reactive
59
why does bonding between polar solves and nucleophiles make the nucleophiles less reactive
the lone pairs of electrons are interacting with the electron-poor hydrogen atoms of the solvent
60
describe nucleophilicity within polar parotid solvents
in polar parotid solvents, nucleophilicity increases going up the periodic table
61
what are the six types of reaction intermediates
- carbon or nitrogen atoms attached to a leaving group
- carbocations
- carbonyl compounds
- alphs-beta-unsaturated carbonyl compounds
- quinones
- epoxides
62
define the relative stability of carbocations
3>2>1>methyl
63
what is found in carbonyl compounds
electrophilic carbons
64
what are quinones
cyclic conjugated dikeytones
65
what are epoxides
statically hindered ethers
66
describe epoxide reactions
all involve nucleophilic attach at the carbon atoms (which leads to opening of the ring)
67
what is the driving force of epoxide reactions
the driving force is the relief of steric strain
68
describe a radical
always have at least one unpaired electron and usually very reactive
69
what radical reaction is least likely to happen
termination
70
define oxidative stress
an excess of prooxidant over antioxidant reactive species
71
what is the result of oxidative stress
-damage to proteins, lipids,nucleic acids
72
why is oxidative stress caused
its the result of exposure to reactive oxygen species
73
explain metabolism
allows the enzymatic conversion of compounds too more polar compounds
74
after metabolism, why are the compounds changed to more polar versions of themselves
to be more easily excreted
75
compare metabolites to the parent compounds
- most metabolites are more water-soluble than the parent compound
- most metabolites tend to be more ionized than the parent compound
- metabolited tend to less active
76
what is a pro drug
therapeutic agents that must be first metabolized to be activated
77
what are proximal carcinogens
chemical carcinogens where the parent compound itself is not carcinogenic
78
where is the primary site of xenobiotic metabolism
the liver
79
explain the first pass effect
when most agents pass through the liver prior to reaching their target site. Results in a portion to be inactivated/activated in the wrong place (liver)
80
what types of reactions are involved in phase 1 metabolism
hydrolysis, oxidations, reduction
81
describe the increase in polarity within phase 1 metabolism
the increase in polarity is small
82
what is the general mechanism of phase 1 metabolism
the exposure of functional groups
83
describe the consequences of phase 1 metabolism
results in metabolic activation
84
what types of reactions are involved within phase 2 metabolism
conjugation
85
describe the change in polarity with phase 2 metabolism
large increase in polarity
86
describe the general mechanism of phase 2 metabolism
polar compounds are added to functional groups
87
what is the consequence of phase 2 metabolism
facilitates excretion
88
what is cytochrome p450 responsible for
responsible for the majority of the biotransformation reactions used to metabolize endogenous and exogenous compounds
89
what is cytochrome p450
microsomal enzymes: membrane-bound vesicles that result from the fragmentation of the endoplasmic reticulum
90
what is the mechanism of cytochrome p450
they catalyst the insertion of one molecule of oxygen into the substrate (one O atom is inserted into the chemical and the other is reduced to form H2O
91
The unusual 450m, absorption is de to
fe(2) binding to cysteine-thiolate
92
what is the MAJOR reaction type in phase 1 metabolism
oxidation
93
what is the MAJOR reaction type in phase 2 metabolism
conjugation
94
which phase 2 reaction increases metabolites stability compared to the parent compound
N-acetylation
95
which phase 2 reason traps reactive intermediates?
glutathione conjugation
96
which amino acids make up glutathione
glutamic acid, cysteine, glyceine
97
in reverse-phase HPLC, the mobile phase typically consists of?
water-acetonitrile
98
in reverse-phase hplc, what would be the expected order of elution in water (pH5)-acetonitrile (phenol, pyrene, toluene, benzoic acid)
benzoic acid, phenol, toluene, pyrene)
99
to be detected in positive mass spectrometry, describe the weight the ions must be
must be heavier than the initial compound
100
to be detected in negative mass spectrometry, describe the weight the ions must be
must be lighter than the initial compound
101
for separation of OTA and its metabolites in reverse-phase HPLC, pH pf the middle phase should be:
1
102
use of gluceronic acid
gluceronic acts is the mail sugar used to prevent the accumulation of waste products of metabolism
103
what us an aglycone
a compound without a sugar
104
what gets added to aglycone to form a gluceronide
UDPGA + aglycone= gluceronide + UDP
105
what prevents hydrolysis by peptidases
peptide linkage
106
what form of GHS is a good nucleophile
ionized thionate form of GHS is a good nucleophile
107
what makes GSH a good reductant
ability of surfer to donate electrons
108
what enables defence against oxidative stress
GSH
109
difference in liquid chromatography and high performance liquid chromatography
- high degree of separation
| - one solvent composition
110
describe a gradient system
- varying eluent composition
- varying solvent composition
- can be either high or low pressure
111
describe an isocratic system
- constant fluent composition
| - one solvent composition
112
benefit to isocratic system
useful if you want one peak and don't care about poor separation
113
benefits to gradient system
good peak separation
114
describe stationary phase in reverse phase chromatography
low polarity
| made of octadecyl group-bonded silica gel (ODS)
115
what is the stationary phase in reverse phase chromatography made of
ODS
116
describe mobile phase in reverse phase chromatography
high polarity
| usually water+acetonitrile
