Principles of Toxicology Flashcards
what does TD50 tell you
median toxic dose
what values are plotted on a graph to show the relationship between exposure and response
response (% of the population) against log10 dose
what does NOAEL stand for
no observed adverse effect level
which sort of toxicants do not have a dose below which no adverse respose is evoked
carcinogens and mutagens
what shape is the curve of a graph showing a toxicant that demonstrates hormesis
U or J
what does a steep slope on the dose/response graph suggest about the toxicant
a small change in exposure ellicits a large change in toxicity ie high affinity toxin
what are the 4 aspects of exposure
route, intensity, frequency and duration
what is meant by bioavaailability
the extent to which a drug or other substance is taken up by a specific tissue or organ after administration
what are the main routes of entry of a toxicant
ingestion and absorption from GI tract, inhalation and absorption from lungs or absorption through skin
what is the key property of a toxicant which determines its ability to be absorbed
lipid solubility
what are the ways in which toxicants can be removed by the body
excretion in urine, bile or exhaled air
by metabolism
accumulation
under what cicumstances does accumulation of a toxicant become threatening
during starvation due to breakdown of fat stores
name an example of a toxicant which is not absorbed by diffusion, but instead is transported
paraquat
does carbon monoxide bind haemoglobin reversibly or irreversibly
reversibly
do organophophate nerve gases bind irreversibly or reversibly to acetylcholinesterase
irreversibly
how does binding of a toxicant to a target cause illness generally
it alters target function and cell homeostasis
under what circumstances is a toxicant less likely to compromise the fntion of a target cell/tissue/organ
if the target can be rapidly regenerated or is well protected
give 2 examples of drugs which elicit hormetic responses
biochanin A and brommodioxyuridine
what is the target tissue of paraquat
lung eputhelia
where is paraquat and other toxins stored when accumulated
fat tissues
give an example of a drug which metabolites are more toxic
paracetamol
how does metabolism increase the ability to excrete toxicants
alters lipid solubility
what are the 4 circumstances of exposure to toxicants
environment
accidental/intentional
treatment of illness
occupational
what are the 4 methods of movement across the epithelia
transcellular (across membrane)
carrier mediated
paracellular (through gaps)
endo/exocytosis
name a toxin which crosses the epithelia via carrier mediated method
arsenic
how is botox transported across the epithelia
endo/exovytosis
how is NOAEL used to calculate the starting dose in clinical trials
NOAEL/100 as 10x more sensitive and 10x slower at removing toxicant than animals
what does the threshold of toxicological concern estimate?
quantitatively estimates the size of the population, the intensity, duration and frequency of exposure and the routes of entry
what must be carried out if exposure is likely to be higher than TTC
further risk assesment
which populations are generally more susceptible to toins
children and elderly
which population are more susceptible to toxicity from acetyl due to 90% of them being fast metabolisers
asian
when is something deemed to be “safe”
if risks are judged to be acceptable
what is REACH
registration, evaluation and authorization of chemicals
when was REACH introduced and who by
june 1st 2000
EU
what is the purpose of REACH
to improve protection, a more transparent system for risk assessment and control of chemicals
does REACH promote non-animal testing
yes
