Midterm Exam Flashcards

0
Q

Definition of environmental toxicology

A

Study of adverse chemical effects on living organisms, communities, populations, and ecosystems.

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1
Q

Definition of toxicology

A

Study of adverse chemical effects on living organisms

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2
Q

Who was the father of modern toxicology, and why was he important

A

Paracelsus. Said that the dose determines the poison. Anything can be toxic; what matters is the dose.

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3
Q

How did the field of toxicology start?

A

Evolution of human culture. Hunters/gatherers, needed to know what could be eaten.

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4
Q

What event completely changed toxicology?

A

The industrial revolution and the advent of organic chemistry. Thousands of new chemicals were synthesized. Today, about 100,000 chemicals have been synthesized.

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5
Q

For what percent of chemicals do we have basic toxicity data?

A

~5%

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6
Q

when did modern toxicology begin?

A

after 1930

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7
Q

Who is the mother of modern environmental toxicology?

A

Rachel Carson. Wrote the book Silent Spring which described the dangers of pesticides (DDT) and biomagnification in the food chain, which was wiping out bird populations.

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8
Q

What is descriptive toxicology?

A

Defines the window of adverse effects. Major tool is the toxicity test.

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9
Q

what is mechanistic toxicology?

A

studies how chemicals get into organisms and produce adverse effects.

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10
Q

what is the LD50?

A

lethal dose where 50% of the population is estimated to die.

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11
Q

what is the window of toxicity?

A

the range where we see adverse effects.

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12
Q

how do you perform a toxicity test?

A

array of beakers with daphnia. give different doses, wait a given amount of time, and count how many die. can also count reproductive output, tumors, etc.

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13
Q

what is the ED50?

A

effective dose where 50% are affected. we aren’t always measuring lethality as our endpoint.

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14
Q

difference between LC50 and LD50

A

dose: concentration that past biological membrane
concentration: amount in environment

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15
Q

what does a dose response curve show?

A

plot of concentration vs mortality.

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16
Q

what is potency?

A

toxicity at low concentrations. more potent= more toxic at low concentrations

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17
Q

what is efficacy?

A

how fully the chemical can affect the population.

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18
Q

what are the three areas of toxicology?

A

descriptive, mechanistic, regulatory

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19
Q

what are some ways that toxic agents are classified?

A

target organs, uses, sources, effects, physical state, chemical stability,

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20
Q

what is an allergic reaction?

A

when an antibody finds antigens that have crossed the biological membrane.

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21
Q

what is an idiosyncratic reaction?

A

an abnormal reaction usually due to variation in individuals. some individuals are hyper-sensitive.

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22
Q

local vs systemic.

A

local: effects right where it occurs.
systemic: toxin crosses the biological membrane, distributes through the body, and that’s where the effects are observed.

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23
Q

what is an additive reaction?

A

no interaction between the chemicals

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24
Q

synergystic

A

if effects are > additive

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25
Q

antagonistic

A

if effects are < additive

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26
Q

functional antagonism

A

function of one compound influences the function of another compound

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27
Q

chemical antagonism

A

A and B undergo a chemical reaction, which changes the effects

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28
Q

dispositional antagonism

A

absorption/distributional phase is affected. ex compounds to induce vomiting

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29
Q

receptor antagonism

A

something comes in and blocks biological receptor.

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30
Q

routes of exposure, from most effective to least effective

A

intravenous, inhalation, oral, intramuscular, intraparateneal cavity, dermal

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31
Q

acute

A

high conc, short-term, mortality is typically the end point

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32
Q

chronic

A

lower conc, longer time, look further than mortality for the endpoint, for example, disease, tumors.

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33
Q

acclimation

A

change in tolerance caused by change in physiology of the individual.

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34
Q

adaptation

A

change in tolerance at the population level, caused by natural selection

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35
Q

frequency

A

increased frequency usually means increased toxicity, although this isn’t always true because of tolerance acclimation

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36
Q

types of transport

A

diffusion, filtration, active transport, secondary active transport, facilitated diffusion

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37
Q

major ABC transporters/proteins

A

MRP and MDR transporters move xenobiotics/toxicants

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38
Q

first pass effect

A

everything from the digestive tract is first brought to the liver, where it is filtered. toxicants are pumped into the bile, which is pumped back into the duodenum for excretion.

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39
Q

factors to consider in lung absorption

A

number of alveoli, membrane thickness. microcillia protect us from particles. if particles enter the alveoli, then they cause an immune response.

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40
Q

methods of excretion

A

urinary, fecal (non-absorbed digesta, biliary excretion)

41
Q

kidney structure (3 nephron regions)

A
  1. filter. Bowman’s capsule, which contains the glomerulus
  2. tube. loop of hence. fine-tuning
  3. duct. collecting duct. water re-absorption
42
Q

function of the liver

A

to remove toxicants. takes on all of the vasculature from the digestive tract. set up as a big filter/sieve. portal triad in conjunction with the liver central vein

43
Q

volume distribution

A

plasma water: water held in blood
interstitial water: water held in tissues
intracellular water: water held in cells

44
Q

factors facilitating distribution

A

porosity of the endothelium
specialized transport
accumulation in organelles
reversible intracellular binding

45
Q

factors opposing distribution

A

binding to plasma proteins (#1 is albumen)
specialized barriers ex. blood-brain barrier, blood cerebral spinal fluid barrier, blood-placental barrier
distribution to storage sites (liver, kidney, bone, fat)
association with intracellular proteins can make it hard to get inside a cell
export from cells

46
Q

what is the purpose of metabolism?

A

to make fat-soluble compounds more water-soluble so that they can be excreted. this is critical because otherwise the compounds would just accumulate in fat.

47
Q

phase 1 metabolism

A

enzyme adds a functional group to compound, which results in small increases in water solubility

48
Q

phase 2 metabolism

A

adds and endogenous substrate to the molecule. results in a large increase in hydrophilicity by producing a water-soluble substrate that s easily excreted.

49
Q

bioactivation

A

when metabolism causes a compound to change into a more toxic form

50
Q

2 main organs active in metabolism

A

liver, kidneys

51
Q

cellular location of phase 1 metabolism

A

ER

52
Q

cellular location of phase II metabolism

A

cytosol

53
Q

microsomes

A

a product that biochemists make from ER

54
Q

phase I reactions

A

hydrolysis, reduction, oxidation

55
Q

phase I functional groups

A

hydroxyl, amine, thiol, carboxylic acid

56
Q

examples of oxidation

A

oxygen addition (sulfoxidation, N-oxidation)
hydrogen removal
epoxidation

57
Q

examples of reduction

A
oxygen removal
hydrogen addition (unsaturated bonds to saturated)
donor molecules (FAD, NADPH)
58
Q

examples of hydrolysis

A

splitting of amide and ester bonds

59
Q

what is the most important phase I enzyme?

A

cytochromes p450. this handles the bulk of the traffic

60
Q

basic reaction of cytochrome p450

A

RH +O2 + NADPH + H+ -> R(OH) + H2O + NADP+

61
Q

Where is the highest concentration of Cytochrome p450?

A

liver, although it is present in virtually all tissues

62
Q

characteristics of cytochrome p450

A

great catalytic versatility and large number of metabolized substrates.
heme-containing proteins. heme iron complex acts as the catalytic center by donating and accepting electrons
end result is that a hydroxyl group is added to the toxicant to make it more water soluble

63
Q

some examples of cytochrome p450 catalysis

A

epoxidation, hydroxylation, dehydrogenation, ester cleavage, desulfuration

64
Q

constitutive p450s

A

constantly being made. only expressed in a few tissues and their activity is relatively constant

65
Q

inducible p450s

A

synthesis is triggered by xenobiotics. enzymatic activity is triggered in response to a substrate until no longer needed, then it returns to baseline levels. responsible for drug/xenobiotic metabolism

66
Q

nuclear receptors

A

relay message to nucleus to start transcribing cytochrome p450. regulatory molecules allow the transcription to be induced.

67
Q

2 main organs active in metabolism

A

liver, kidneys

68
Q

cellular location of phase 1 metabolism

A

ER

69
Q

cellular location of phase II metabolism

A

cytosol

70
Q

microsomes

A

a product that biochemists make from ER

71
Q

phase I reactions

A

hydrolysis, reduction, oxidation

72
Q

phase I functional groups

A

hydroxyl, amine, thiol, carboxylic acid

73
Q

examples of oxidation

A

oxygen addition (sulfoxidation, N-oxidation)
hydrogen removal
epoxidation

74
Q

examples of reduction

A
oxygen removal
hydrogen addition (unsaturated bonds to saturated)
donor molecules (FAD, NADPH)
75
Q

examples of hydrolysis

A

splitting of amide and ester bonds

76
Q

what is the most important phase I enzyme?

A

cytochromes p450. this handles the bulk of the traffic

77
Q

basic reaction of cytochrome p450

A

RH +O2 + NADPH + H+ -> R(OH) + H2O + NADP+

78
Q

Where is the highest concentration of Cytochrome p450?

A

liver, although it is present in virtually all tissues

79
Q

characteristics of cytochrome p450

A

great catalytic versatility and large number of metabolized substrates.
heme-containing proteins. heme iron complex acts as the catalytic center by donating and accepting electrons
end result is that a hydroxyl group is added to the toxicant to make it more water soluble

80
Q

some examples of cytochrome p450 catalysis

A

epoxidation, hydroxylation, dehydrogenation, ester cleavage, desulfuration

81
Q

constitutive p450s

A

constantly being made. only expressed in a few tissues and their activity is relatively constant

82
Q

inducible p450s

A

synthesis is triggered by xenobiotics. enzymatic activity is triggered in response to a substrate until no longer needed, then it returns to baseline levels. responsible for drug/xenobiotic metabolism

83
Q

nuclear receptors

A

relay message to nucleus to start transcribing cytochrome p450. regulatory molecules allow the transcription to be induced.

84
Q

phase II metabolism

A

conjugation reactions. add an organic molecule to a xenobiotic to make it more soluble, recognizable, and easily excreted.

85
Q

two types of conjugation reactions

A

type I: xenobiotic + reactive conjugating ligand->conjugated product

type II: reactive xenobiotic + conjugating ligand -> conjugated product

86
Q

examples of type I conjugation rxn

A

methylation(has CH3 attached to S), sulfating (has sulfate group attached), glucuronidation (has ring attached), acetylation(has O=CCH3 attached)

87
Q

examples of type II conjugation rxn

A

amino acid conjugation (has H2N attached), glutathione conjugation (has SH attached)

88
Q

cofactors required for type I

A

reactive/activated cofactor

ex. UDP, PAPS, acetyl CoA, SAM

89
Q

cofactors required for type II

A

reactive xenobiotic

ex. glutathione, amino acids (glycine, glutamine, taurine)

90
Q

what is the most important and widespread form of conjugation?

A

glycoside formation

glucoronidation and glucosidation

91
Q

glucoronidation is a major pathway in vertebrates excepts for what animal?

A

cats!

92
Q

what is a major pathway in plants and invertebrates?

A

glucosidation

93
Q

what affects glucoronide excretion?

A

the molecular weight determines if it will be excreted through the urine or through the bile. MW cutoff is somewhat species dependent

94
Q

what are some genetic and developmental deficiencies?

A

deficiency in glucoronidation causes predisposition for jaundice, increased risk of toxicity fro drugs. gilbert’s disease, criglar-Najjar syndrome

95
Q

sulfate conjugation (sulfation)

A

biotransforms xenobiotics as well as endogenous compounds
excretion of thyroid and steroid hormones

activity is low in pigs, high in cats.
higher in males than females

96
Q

methylation

A

common but minor pathway
makes substrate less water soluble and masks available functional groups for conjugation
occurs in the cytosol, uses metals
guinea pigs have unusually high capacity to methylate

97
Q

acetylation

A

major route for xenobiotics containing an aromatic or hydrazine group
cytosolic
wide species variability
there are fast and slow acetylators

98
Q

amino acid conjugation

A

amino acids = glycine, glutamine, arginine, and taurine in mammals and primates, ornithine in reptiles and birds
activity herbivores> omnivores>carnivores

99
Q

what is the most important phase II enzyme system?

A

glutathione.

binds extremely reactive intermediates, plays an extremely protective role in the cell.