HC1: Introduction on toxicology
Public interest on the effects of pollution is still growing.
Toxicology = the study of the adverse effects of chemicals on living organisms.
Toxicology testing is done to determine the degree by which a substance damages organisms (how
toxic is this compound to e.g. worms).
Different types
o Mechanistic toxicology = identifies the cellular, biochemical and molecular mechanisms by
which chemicals exert their toxic effects.
o Descriptive toxicology = focused on toxicity testing to provide information on safety
evaluation and regulatory requirements.
o Regulatory toxicology = the responsibility to decide is a drug or another chemical is of
sufficiently low risk to be marketed for a stated purpose.
Toxicology was started by Socrates
Was sentenced to die by taking poisoness hemlock. People started to think about how this could kill
him.
All substances are poisons, the dose separates a poison from a remedy.
o Salt, silicon (breast implants), water, etc. can also be toxic.
o Make-up, fragrance, paint (not anymore), etc.
o Things are starting to change trying to find alternatives for the things we use now to make them
less toxic.
2 types of toxic effects
Systemic toxicity
o Affects whole body.
Organ specific toxicity
o Chemicals cause major toxicity to one or two organs. Reproductive toxicity, hepatoxicity,
nephrotoxicity, etc.
Dose-response curve
LD50 > lethal dose (concentration at which 50% of the population dies)
LC50 > lethal concentration
NOEC > no observed effect concentration
LOEC > lowest observed effect concentration
Etc
KNOW THE UNITS
o Big impact on survival, don’t want to confuse them.
o The lower the endpoint value (the closer to 0), the more toxic a chemical is (need less to have a
lethal dose).
,HC2: Toxicology
Survival > dichotomous (either dead or alive)
Enzyme activity > continuous (anywhere from 0 to 100)
How many doses do we need to get a dose-response curve?
3 is the minimum, might not be a curve yet (more a straight line). The more points you have
(doses you’ve tried), the better the graph becomes.
LC50, EC50, ECx are all determined by the statistics
o If the dose is not tried, the number is based on the line created by a computer (the curve)
o LOEC and NOEC are not determined by statistics, but by the tested concentrations.
What do we use the curves for?
Predict the effect of a specific toxicant concentration.
Backwards use
o Estimate the exposure that triggers a response. E.g. effective dose is 0.1 micromolar,
anything above is toxic.
Dose-response relationships
1. Can see the potency
, 2. Maximum response (how effective it is)
3. Slope of the curve (how quickly will a reaction happen)
Can only do a comparison between the potency if the curves have the same slope and reach the same
maximum response.
Which is most potent > A.
Can compare all the graphs because they have same slope and efficacy. EC50 is higher for A, so
need more of D to reach an effect. Increasing potency means a lower EC50.
The relative potency (REP) = EC 50 [standard] / EC50 [test]
THESE QUES TIONS MIGHT BE IN EXAM!!!
Have to say “A is 11 times more potent than C”. just saying 11 doesn’t say anything. No units for this.
Higher efficacy means it is more toxic.
Therapeutic index = dose-response for the drug having a positive effect (what you need it for).
The larger the TI, the safer the drug is.
TI = LD50/ED50
, High TI drugs (e.g. paracetamol) are safer to use, because there is a bigger window to get the
dosing right. Low TI drugs (e.g. chemo) are less safe, because you’re balancing on a thin line
between safe and toxic effect.
Window of causality
We need essential trace metals (iron, zinc, magnesium, cobalt, nickel, etc) for survival.
o In the middle is what you need. If you don’t have enough, you have a deficiency. Can still
survive, just QoL is a bit less. Too much is toxic. Need an optimal balance.
o Not the same for heavy metals that are toxic (led, silicon, cadmium, etc). these are non-
essential trace metals. We are exposed to these a lot.
Evidence shows if you have a deficiency in essential metals is associated with adverse
pregnancy outcomes.
Don’t vape, will kill you.
Once you get to 200 clicks, metals are quite high and become toxic. Don’t know the long-term effects
yet. Can effect a lot of things.
What do we look for in a DR-curve
Public interest on the effects of pollution is still growing.
Toxicology = the study of the adverse effects of chemicals on living organisms.
Toxicology testing is done to determine the degree by which a substance damages organisms (how
toxic is this compound to e.g. worms).
Different types
o Mechanistic toxicology = identifies the cellular, biochemical and molecular mechanisms by
which chemicals exert their toxic effects.
o Descriptive toxicology = focused on toxicity testing to provide information on safety
evaluation and regulatory requirements.
o Regulatory toxicology = the responsibility to decide is a drug or another chemical is of
sufficiently low risk to be marketed for a stated purpose.
Toxicology was started by Socrates
Was sentenced to die by taking poisoness hemlock. People started to think about how this could kill
him.
All substances are poisons, the dose separates a poison from a remedy.
o Salt, silicon (breast implants), water, etc. can also be toxic.
o Make-up, fragrance, paint (not anymore), etc.
o Things are starting to change trying to find alternatives for the things we use now to make them
less toxic.
2 types of toxic effects
Systemic toxicity
o Affects whole body.
Organ specific toxicity
o Chemicals cause major toxicity to one or two organs. Reproductive toxicity, hepatoxicity,
nephrotoxicity, etc.
Dose-response curve
LD50 > lethal dose (concentration at which 50% of the population dies)
LC50 > lethal concentration
NOEC > no observed effect concentration
LOEC > lowest observed effect concentration
Etc
KNOW THE UNITS
o Big impact on survival, don’t want to confuse them.
o The lower the endpoint value (the closer to 0), the more toxic a chemical is (need less to have a
lethal dose).
,HC2: Toxicology
Survival > dichotomous (either dead or alive)
Enzyme activity > continuous (anywhere from 0 to 100)
How many doses do we need to get a dose-response curve?
3 is the minimum, might not be a curve yet (more a straight line). The more points you have
(doses you’ve tried), the better the graph becomes.
LC50, EC50, ECx are all determined by the statistics
o If the dose is not tried, the number is based on the line created by a computer (the curve)
o LOEC and NOEC are not determined by statistics, but by the tested concentrations.
What do we use the curves for?
Predict the effect of a specific toxicant concentration.
Backwards use
o Estimate the exposure that triggers a response. E.g. effective dose is 0.1 micromolar,
anything above is toxic.
Dose-response relationships
1. Can see the potency
, 2. Maximum response (how effective it is)
3. Slope of the curve (how quickly will a reaction happen)
Can only do a comparison between the potency if the curves have the same slope and reach the same
maximum response.
Which is most potent > A.
Can compare all the graphs because they have same slope and efficacy. EC50 is higher for A, so
need more of D to reach an effect. Increasing potency means a lower EC50.
The relative potency (REP) = EC 50 [standard] / EC50 [test]
THESE QUES TIONS MIGHT BE IN EXAM!!!
Have to say “A is 11 times more potent than C”. just saying 11 doesn’t say anything. No units for this.
Higher efficacy means it is more toxic.
Therapeutic index = dose-response for the drug having a positive effect (what you need it for).
The larger the TI, the safer the drug is.
TI = LD50/ED50
, High TI drugs (e.g. paracetamol) are safer to use, because there is a bigger window to get the
dosing right. Low TI drugs (e.g. chemo) are less safe, because you’re balancing on a thin line
between safe and toxic effect.
Window of causality
We need essential trace metals (iron, zinc, magnesium, cobalt, nickel, etc) for survival.
o In the middle is what you need. If you don’t have enough, you have a deficiency. Can still
survive, just QoL is a bit less. Too much is toxic. Need an optimal balance.
o Not the same for heavy metals that are toxic (led, silicon, cadmium, etc). these are non-
essential trace metals. We are exposed to these a lot.
Evidence shows if you have a deficiency in essential metals is associated with adverse
pregnancy outcomes.
Don’t vape, will kill you.
Once you get to 200 clicks, metals are quite high and become toxic. Don’t know the long-term effects
yet. Can effect a lot of things.
What do we look for in a DR-curve
