Toxicology Flashcards
What is toxicology?
The science of poisons
Studies the adverse responses in biological systems caused by a chemical or physical agent
What are the 2 main aspects of toxicology?
- basic science
o study the nature and mechanism of the adverse effect - risk assessment
o assess the likelihood of occurrence of an adverse effect
Paracelsus, principle?
The dose makes the poison, (the treatment for syphilis, the right dose is a treatment but in high doses it is bad)
Types of toxins?
Fungi: mycotoxins
Plants: phytotoxins
Animals: animal toxins
What is Foxglove used for?
Foxglove – phytotoxins (from plants)
The right dose helps with myocardial contractions
But in high doses causes death
Most plants are poisonous, daffodils?
Daffodils (competitive inhibitor of acetylcholinesterase (breaks down acetylcholine))
The galantamine in daffodils blocks acetylcholinesterase, its calcium oxalate crystals also irritate the mouth
What do cardiac glycosides do?
Inhibits the Na+/K+ pump, cardiac myocytes gain Ca2+ via Na/Ca exchange, increase their contractibility, risk of arrythmia
Oleander plant is toxic?
Oleander plant: one leaf will kill you, has cardiac glycosides
Why is ricin toxic?
Ricin blocks protein synthesis
1mg of ricin will kill a human
Where is ricin found?
in castor beans (not their oil though)
How does ricin prevent protein synthesis?
- 2 units A and B
- Linked by disulfide bond (very strong)
- The B unit recognizes the cell membrane and inks to it, to get the toxin into the cell
- The A unit is released in the cell and attacks ribosomes where proteins are made,
- Inactivates the ribosomes
- Highly toxic
- One cell after another dies
What toxin is in pear seeds?
Formaldehyde
What toxin is in potato skin?
Solanine
What are some toxic components in plastic, where can they end up?
Plastics contain toxic compounds, lead, mercury, arsenic
Its hard to recycle its components
When plastics are discarded: they can end up in the water, soil, air, rain,
What is most frequently involved in human poisonings?
Drugs,
Children consuming bad things
Deaths from opioids moved up the list, acetaminophen alone too
Children accidental poisoning (1-2years old) then it is deliberate (suicide)
Fertility can be impacted by pollution?
Health effects of pollution
Soil contamination, water contamination, air pollution (what we breath can go everywhere, we can absorb small particles from our lungs)
Chronic toxicity: bigger problem than acute poisoning, examples of chronic toxicity?
- Smoking
- Air pollution
- Unsafe water
- Chronic drug use
Air pollution?
Air pollution: NOx, SO2, CO2, Mercury (we have many testing facilities in Montreal)
When you breath all the things in the air can get to your lungs, heart, and brain
Large particles trapped in the upper airways, but smaller particles can get further into the lungs, and tiny particles can get into the bloodstream, or phagocytosis, macrophages transport, if the particles get into the brain there can be impaired development, dementia
Routes for pollutants to enter the brain? (3)
- Olfactory bulb
- Alveoli – blood
- GI tract, direct/microbiome (can affect circulation of toxins)
What is Environmental toxicology?
Environment affects potential absorption of toxicants
How can bioavailability change?
Bioavailability varies with location (in water)
What is biomagnification?
Biomagnification of food chain: DDT concentrations increases in water, then to small fish, then big fish, then birds eat the big fish and caused a near extinction of bald eagles since their eggshells got very fragile, so baby birds were not surviving)
accumulation of toxins as go higher up the food chain
What is the therapeutic index?
Evaluating safety: dose response curves with LD50, LD10, margin of safety = LD0.1/ED90
Why is it important to look at the full shape of the dose response curve?
Therapeutic and toxic curves may not be in parallel, it can be misleading therefore need to look at the full shape of the curve to determine safety
Ideally want the therapeutic effect 100% with little to no toxic dose and no lethal dose
What drug has not threshold dose?
Nicotine
What is NOAEL?
NOAEL: highest data point where no observed toxic/adverse effect in seen
What is LOAEL
LOAEL: lowest observed adverse/toxic effect level (lowest dose with an adverse effect)
What is hormesis?
Drugs can either be beneficial as they increase or cause dysfunction as they increase but then become beneficial at a higher level
As vitamins increase in dose their effect is better, but overdose causes impaired health and then becomes toxic
Too little antibacterial drug given promotes resistance (a problem), but increasing the dose gets rid of the bacteria causing a positive effect
Animal testing?
Strict regulations for animal treatment in research
More animals are killed for food or in roadkill than killed in research
Can warfarin be used to kill rats?
Montreal rat problem: warfarin – kills rats quickly and painlessly, internal bleeding causes them to get thirsty and go down to the sewer to get water where they will die
Types of observational studies?
- Cohort
- Case control
- Cross-sectional
What is a cohort study?
- A group of people are exposed or not to a drug and follow the observed disease
- Retrospective; compares previous exposure
- Prospective; compare future exposure
What is a case control study?
- People with a problem and compare to people with no problem in the same environment
What is a cross-sectional study?
- Gather data on exposure and disease,
- Try to find links between people
- Looks at the exposure and the outcome at the same time
large group, ask them questions about lifestyle and see what you can make out of it
What do epidemiology studies measure?
Epidemiology studies measure the risk of illness or death in an exposed population compared to that risk in an identical unexposed population
Epidemiology studies need to be?
- Well constructed: same age, sex, lifestyle
- Bias free: selection bias causes groups to not be comparable, information bias
- Confounding: control other factors
Risk assessment vs risk management?
- Hazard identification
- Government agencies need to make a decision on banning things
Costs money: will 1 million dollars help save 2 people vs 100 people, maybe the money could be better spent elsewhere
Lead is present in?
Lead is present in buildings, paint, lead from soil, Lead in gasoline, paint, food cans, lead in the air
What effect can lead toxicity have?
Toxic to adults and children
2002, lead recall for toys
Effect on development, intellectual growth, brain development in kids
Lead toxicity symptoms?
Symptoms: neurological, gastrointestinal
No safe exposure levels in children, impaired at low levels
Blood lead levels are lowered there is a higher IQ
Lead pharmacodynamic effect?
Lead alters the time of divalent cations, mainly Ca2+, affecting ion channels
It blocks excitatory glutamate receptors
Enters cells, alters many functions
Big effect on neurons
alters presynaptic transmitter release, blocks postsynaptic NMDA receptors
Pharmacokinetics of lead?
- Breath in, get into blood, accumulates in the bone and can leach out again
Where is mercury found?
Can accumulate in water
Many sources: soil, volcanoes, industry
Biomagnification of mercury?
Mercury gets methylated, rises up the food chain, bioaccumulation, since it does not biodegrade
Biomagnification of methylated mercury
(tuna we eat, mercury gets into our bodies, organs)
Long term exposure to mercury?
Long term – deterioration of the nervous system
What is the grasshopper effect?
Grasshopper effect: every season toxins move up and down and there is a bioaccumulation towards the north, in northern animals (polar bears)
What are persistent organic pollutants?
Persistent organic pollutants – don’t stay in one place, move around the globe
Pesticides/herbicides used for?
Farmers need to use them to protect their crop from weeds, diseases, insects
Pesticides/herbicides mechanism of action?
Their mechanisms of action are diverse
Inhibit photosynthesis…
What human diseases has insecticide reduced?
malaria, yellow fever, plague, African sleeping sickness
DDT-organochlorine consequences?
- Save million of lives
- Get to food chain, birds have thin eggshells, can’t reproduce properly
- Acts on voltage gated Na+ channels
- Widely used in developing countries
What is lidane?
It is used to get rid of lice
Pyrethroids (insecticides) mechanism of action?
Pyrethroids: insect voltage gated ion channels are different than human ones
Causes insects Na+ channels to open for longer causing insects to convulse and die
What is malathione?
It is an organophosphate insecticide, acetylcholinesterase inhibitor, it is least toxic to mammals because we can metabolize it
it acts at the neuromuscular junctions and causes death from respiratory failure in insects.
