Principles of Toxicology Flashcards
What do many chemicals require to be harmful
access to the internal environment
what are the main routes of toxicant entry into the body?(3)
GI tract, respiratory and skin
example of two biological targets
enzymes and transport proteins
what does carbon monoxide bind with high affinity to
haemoglobin
where is paraquat concentrated
in its target cells within the lung
what is TD50
the median toxic dose or concentration
what is LD50
the median lethal dose or concentration
what does NOAEL stand for
no-observed-adverse-effect level
what are quantal responses?
all-or-none, they have two outcomes
can you define a threshold dose or concentration below which there is no detectable biological response?
yes
what is used in the risk assessment of chemicals
threshold of toxicological concern
what is the threshold of toxicological concern
a level of exposure to chemicals below which there would be negligible risk to human health
how can NOAEL be used to determine the reference dose/exposure
divided by 100
what aids the determination of NOAEL
exposure-response studies
what are the starting points for hazard recognition
data from in silico and in vitro studies
what is the EU regulatory framework for chemicals known as
REACH
what does REACH stand for
registration, evaluation and authorisation of chemicals
what does REACH aim to do?
identify properties and hazards of chemicals before they harm people
what are reference doses
estimates of the daily exposure to an agent that is assumed to not cause adverse effects on human health
how do you work out the reference dose
NOAEL/ safety factor
what may reference doses be used to estimate
threshold of toxicological concern
what shape are hormetic exposure-response curves
U or J
are hormetic exposure-response curves biphasic?
yes
what may be experienced at high levels of exposure in hormetic curves
negative effects
what does biphasic mean
having two phases
define hormesis
biphasic dose response to an environmental agent characterised by low dose stimulation and high dose inhibitory effect
what is an example of hormesis
effect of alcoholic beverages
what must be considered in risk analysis
socio-economic benefits
can absolute safety ever be guarenteed
no
how is risk sometimes expressed
hazard x exposure
what are the three routes of entry
ingestion through GI
inhalation and absorption through lungs
tropical and absorption through skin
define bioavailability
the proportion of a drug or other substance which enters the circulation when introduced into the body and so is able to have an active effect
if a chemical is poisonous at point of contact it is known to be
corrosive
what makes a substance a toxicological concern
if it is highly lipid soluble and if exposure to that substance is significant
what two factors for diffusion in the gut, small intestine and lungs
transcellular and lipid soluble
what occurs if the toxicant reaches the target, 4 things
- disruption of homeostasis
- cell death
- organ/tissue dysfunction
- irreversible changes to DNA/chromosomes
what happens to try and stop the effects when a toxicant reaches its target
stress activated protein kinases
what is the down side of stress activated protein kinases that respond to toxicant reaching its target
there is only a limited ability of stress response
define hazard
the potential to cause harm
define risk
the probability that harm will occur
why is risk of toxic exposure high for us
because we do not know enough about chemicals
what is a graded response
a response that has varying degrees of damage
when was REACH introduced
2007
what is the Ames test
test to determine the mutagenic activity of chemicals
what are the shapes of most log-dose curves
sigmoidal
where in a sigmoidal curve is the NOAEL taken from
threshold region
