Toxicology Flashcards
1
Q
what is toxicology?
A
the study of adverse responses in biological systems caused by chemical or physical agents
2
Q
what are the two main aspects of toxicology?
A
the basic science (the nature and mechanisms of effect) and risk assessment (likelihood that effect will occur)
3
Q
what is the overall principle of toxicology?
A
the dose makes the poison
4
Q
what are the different types of toxins?
A
- phytotoxins
- mycotoxins
- animal toxins
- synthetic toxins
5
Q
what are mycotoxins?
A
a natural toxin produced by fungi
6
Q
what are phytotoxins?
A
a natural toxin produced by plants
7
Q
what is a natural toxin? what are the different types?
A
- a toxin produced by living systems for self defense
- mycotoxin, phytotoxin, animal toxin
8
Q
what toxins are present in daffodils?
A
- galantamine, which is found in the bulb
- calcium oxalate crystals in the stem
9
Q
what does galantamine do?
A
- is a competitive inhibitor of acetylcholinesterase, which usually breaks down acetylcholine
- since ACh cannot be broken down, the synapses are flooded with ACh, which can paralyze you
10
Q
what do calcium oxalate crystals do?
A
they irritate
11
Q
what do lily of the valley contain? what can this cause?
A
- contain lycorine poison and glycosides
- can cause cardiac arrythmia and stop the pumping mechanism of the heart
12
Q
what do cardiac glycosides do?
A
- inhibit the Na/K pump
- so cardiac myocytes gain Ca+
- increases contractibility and risk of arrythmias
13
Q
what does the oleander plant contain?
A
cardiac glycoside in high concentration in the leaves
14
Q
where is ricin found?
A
castor oil beans
15
Q
what are the two components of ricin and what do each do? how are they linked together?
A
- A: active – inactivates ribosomes so disrupts protein synthesis
- B: allows it to enter cells
- linked together by disulfide bond
16
Q
how potency of ricin (what is lethal dose)?
A
very potent, only ~1mg needed to kill adult
17
Q
animal toxins tend to target which systems? what are the names of the types of toxins?
A
CV (cardiovascular toxin) and nervous (neurotoxin)
18
Q
what are man-made toxins?
A
toxins that we as humans release into the environment
19
Q
where do man-made toxins end up? how does this occur?
A
- they gradually leak into the soil and water, which can then spread to different places
- can also get into air, and can then be deposited with rain somewhere else
20
Q
poisoning are usually due to what?
A
drugs
21
Q
what is household toxicology?
A
toxins that can be anywhere in the house
22
Q
deaths are more often from ____ that are consumed ______ (for children)
A
drugs ; in the house (for children specifically)
23
Q
people usually wash their fruits and vegetables because they want to wash away __________ but we should also worry about __________
A
- pesticides
- possibility of viruses and bacteria due to high handling
24
Q
Diet: the large amount of ____________ can be viewed as a toxin?
A
salt, saturated fats, and additives
25
toxicity to the unborn: toxicants cane affect ______________ as well as _____
- male and female fertility
- the fetus
26
what are the major ways we are exposed to pollutants?
- soil
- air
- water
27
which body parts can pollutants affect? what are the major ones?
- can affect basically anything in the body
- mainly CV and nervous
- we are sensitive in the GI tracts, so can also cause nausea and enteritis
28
what is the major source of pollution in developed vs undeveloped countries?
- developed usually air since water monitored closely
- undeveloped: water
29
which causes more deaths/sickness: chronic or acute toxicity?
chronic
30
what is the effect of breathing in fine particles?
damage to the heart, lungs, and brain
31
can our body eliminate fine particles when we breath them in? How or why not?
only some of them:
- the larger ones get trapped on the muco-ciliary blanket so get eliminated more easily
- smaller ones can go down to the distal airways and can be phagocytosed by alveolar macrophages
- but, ultra-fine particles can diffuse through alveoli and can go to capillary and get transported everywhere in the body, including the brain
32
ultra-fine particles are said to have what affect on children?
impaired development
33
what are the different route of entry for fine particles into the brain?
- alveoli to blood
- olfactory bulb
- from GI, which can then affect the microbiome
34
What an important concept in environmental toxicology?
The environment in which the toxicant is present
affects how much of it can be absorbed
35
The _______ of a toxin varies with the location.
bioavailability
36
What is biomagnification?
How a toxicant builds up as it goes up a food chain (ex: they can buildup in sediments and mussels can take them up, then they get eaten by other animals, etc)
37
What is the LD-50 of Botulinum toxin
0.0001mg/kg
38
What is the therapeutic index?
distance between the toxic/lethal dose and the therapeutic dose (LD50/ED50 or TD50/ED50)
39
What is LD50?
dose that kills 50% of the population;
40
What is TD50?
dose that causes 50% of the population to be sick
41
What is the margin of safety?
LD01/ED99 the larger the difference, the safer the drug.
42
What is NOAEL and LOAEL? What about the space between them?
- NOAEL is the highest data point at which you see no
observed adverse effects of the substance. Anything
below is safe. (No observed adverse effect level)
- LOAEL is the lowest data point at which there are
observed adverse effects of the substance. Anything
above is harmful. (Lowest observed adverse effect level)
- Anything in between is unknown and further studies
are necessary.
43
What is a hormesis? Give examples.
- change in the effect of a drug when you move from low to moderate doses of the drug
- vitamins: harmful when dose too high
- antibiotics: harmful when dose too low
44
__________ conducted in humans to understand toxicants in different areas of the world.
Epidemiological studies
45
What do observational studies look at regarding toxicity?
measure the risk of illness or death in an ‘exposed population’ compared to a ‘non-exposed
population.’
46
What are the three different types of observational studies?
- cohort
- case control
- cross-sectional
47
What is a cohort study? What are the two types/methods of cohort studies?
- Sample a group of people who are exposed to a certain chemical, you can follow these two groups (exposed and not exposed) over time to compare disease occurrence.
- prospective study: the two groups are monitored for some time: which group will get disease(s) and which will not? It is more accurate, as you follow these people with time
- retrospective: less accurate and faster: just looking at these two groups at one point in time and seeing which one has disease(s)
48
What is a case control study? What method is used?
- You take people with a certain disease and try to find out the cause, so you ask them what they have been exposed to and you try to find what is common to all these people
- always retrospective
49
What is a cross sectional study?
Start with a defined population, such as the population of Canada. You collect data on everything: what diseases the have, what they do for a living, what they are exposed to, etc. and try to see what they have in common.
50
What is the odds ratio?
The risk of disease in the exposed group vs. the non-exposed group
51
What is a standard mortality ratio?
The relative risk of death based on a comparison of an exposed
to a non-exposed group.
52
What is relative risk ratio?
Similar concept as SMR but looking at risk of disease rather than risk of
death
53
What are reasons why there might be variation between different epidemiological studies?
- bias: People are looking for a certain result, so they’re biased in selecting participants for the study. We tend to have preconceived ideas.
- confounding: A factor that the researchers didn’t control for/ account for.
- chance: the researchers did try to control
for the demographics of the sampled groups, but the demographics were not identical.
54
What question is asked when looking at hazard identification? Which studies are used for this?
- what adverse effect(s) does the agent cause, if any?
- Epidemiological studies; toxicologic studies; biological, medical, physical science, and other studies.
55
What are the components of health risk assessment?
- hazard identification
- dose-response assessment
- exposure assessment
56
What are the main targets of lead?
CV system, nervous system, but also kidneys and GI tract are sensitive.
57
______ are more susceptible to lower doses of lead
Children
58
What are the short-term effects of lead poisoning for adults? What happens when it gets worse?
- short-term causes psychological and mental changes, GI issues, fatigue,
and irritability. Vague symptoms at first
- When it gets worse, there are more CNS effects,
neurological symptoms, and effects on joints, especially ankles and wrists.
59
what are the safe levels of lead for children?
there are no safe levels
60
what are the effects of lead on children?
- hearing
- brain
- nerve damage
- impaired intellectual function
- digestive issues
- stunted growth
61
what are the pharmacodynamics of lead in adults and in children?
adults
- blocks calcium signaling
- blocks NMDARs
- has effect on mGLURs
- can affect mito and gene transcription
children:
- impairs synaptogenesis
- apoptosis in neurons
- hyperexcitability
62
why are the pharmacokinetics of lead complex?
since can be taken up by dust, air, soil, paint, water, so can be absorbed from lungs or GI
63
how long does elimination of lead takes? why?
long time since stored in bones and can sometimes be mobilized
64
how does mercury get into our environment?
released from volcanoes and released from various industries, then gets into atmosphere, and it can runoff from land into water
65
which is more toxic mercury or methyl mercury (how is the latter made)? why is it more toxic?
- methyl mercury, which can be methylated in water and one land
- more toxic since is not biodegradable so bioaccumulates
66
what is the grasshopper effect? what effect does this have on mercury toxicity?
- air rises in hotter regions, when seasons change, air masses move north as the temp. cools, then contaminants are washed to the ground and settle
- there is a lot of bioaccumulation in the north with magnification as we go up food chain
67
other than mercury, what compounds can have a grasshopper effect?
persistent organic pollutants
68
what is the effect of herbicides on humans?
skin irritations
69
what are the different mechanisms of action of pesticides?
- inhibit cell division, protein, and carotenoid synthesis, and photosynthesis
70
in what way are insecticides beneficial?
decrease some human diseases that can be carried by insects (e.g. malaria, yellow fever, plague, ...)
71
what are the criteria for ideal pesticides?
- very low toxicity (to humans)
- want them to auto-degrade (little persistence in environment)
- only target the organism you want
- don't want insects to develop resistance
72
are pesticides equally harmful to different species?
no
73
lipophilic chemicals accumulate _____
in body fat
74
why do we have to be careful where we apply pesticides?
since can go in waterways as runoff and can also evaporate in air
75
DDT is an __________ pesticide
organochlorine
76
in what way was DDT beneficial?
- warded off insects that carry diseases
- in WWI, got rid of lice and mosquitoes with diseases
77
how does DDT affect birds?
eggshells were more fragile, so babies didn't survive
78
what do organochlorides do?
- act on voltage-gates Na+ channels
- causes hyperexcitability by causing channels to be open for longer
79
what is Lindane and what does it do?
- pesticide
- blocks inhibition in bugs like termites (convulsions)
80
what are pyrethroids and what do they do?
- insecticide
- act on voltage-gates Na+ channels
- causes hyperexcitability by causing channels to be open for longer
81
what do organophosphate insecticides do?
- blocks breakdown of ACh by blocking acetylcholinesterase
- irreversibility bind to acetylcholinesterase
82
death from organophosphates is due to ________
respiratory failure
83
what is malathion? is it toxic to mammals?
- organophosphate insecticide
- less toxic than others since can metabolize it
