Topic 2: Toxicology Concepts
Environmental Challenges and Defense Systems
ï· Discuss the 2 types of environments we have to be aware of when we're studying
environmental health. How do they relate?
o The two types of environment:
ï· External environment (what we normally think of): everything that is not
ï· Internal environment (that which occurs within the individual person):
because people and their bodies aren't just one big blob of tissue - there
are many processes which go on inside us, and we need to consider how
toxicants can affect that
o The environments are related through the concept of ABSORPTION, which is
the extent to which some toxicant from the EXTERNAL environment can enter
into our internal environment
ï· What are the different challenges which can present themselves in either environment,
and what are the defense systems which our body has for each challenge?
Physical challenge: like getting hit by a bus -- they are hazards that we can see
(usually), although some are invisible such as radiation
ï· So our defense is things like avoidance, adrenaline, etcâ¦which on a
biological level means neuroendocrine defenses, i.e. epinephrine,
Microbial challenges: things like HIV, SARS, pandemic avian flu
ï· These are first handled at the external membrane barrier -- skin, etc.
ï· And then inside us we have general/innate and immunity
o Chemical challenges: similarly to microbial challenges, there are external barriers
in our body for the chemicals we encounter in the environment
ï· Our defense is then external barriers...
ï§ i.e. We could breathe something into our lungs and the lungs are
the barrierâ¦or even our GI tract
ï· â¦and then toxicological defenses, which are frequently biochemical in
nature (analog of immune system for microbial challenges)
ï§ Xenobiotic metabolism is a big issue here, because it studies the
way that the body reacts with foreign chemicals which have
ï· Speaking of xenobiotic substances, what are some sources of xenobiotic exposure?
Pollution, drugs, plant products
ï· Define the following terms: endogenous, exogenous, xenobiotic, contaminant, toxicant,
anthropogenic. Comment where appropriate.
o Endogenous (intrinsic): denotes a substance made within the body
ï· Since the body makes these, they are in GENERAL (but not always)
beneficial to the body
o Exogenous (extrinsic): denotes a substance entering from outside the body
i.e. It comes from the EXTERNAL environment
o Xenobiotic: any exogenous substance not normally found in the body (note that it
doesn't mean DANGEROUS!)
o Contaminant: any exogenous xenobiotic that is considered undesirable
ï· We have to be careful with this word, because "undesirable" does not
mean "toxic" -- it just means undesirableâ¦so beware the difference! o Toxicant: a xenobiotic contaminant that is potentially hazardous to health
ï· So this is a much tighter definition than "contaminant": here we know
that it is CERTAINLY bad
ï· One note here is that since a toxicant is a xenobiotic, it is by definition
something that is created biologically -- and so when the word "toxicant"
or "toxin" is used, it should only refer to biologically created substances
o Anthropogenic: any substance produced by human activity (good or bad)
ï· There is a fallacy here: one of the things that many environmental
advocates still believe or say is that anthropogenic substances are more
hazardous than other types i.e. xenobiotic -- AND THIS IS FALSE
ï§ ESPECIALLY BAD when the word "natural" is used and it
seems like it is "better" and "not dangerous" -- this just isn't true
ï§ There are good, medium, and bad anthropogenic substances just
as there are good, medium, and bad xenobiotic ones
Flowchart for Toxins
ï· Give a word flow-chart for how a xenobiotic substance gets into our body. For each step,
describe the type of analysis which is performed (if applicable).
o Xenobiotic in environment -> exposure -> toxicokinetics/pharmacokinetics ->
ï· Exposure: as discussed before, there are multiple ways in which this can
ï· Toxicokinetics: the pathways by which the toxicants are processed,
metabolized, distributed, etc.
ï§ A SYNONYM for this is pharmacokineticsâ¦although it is more
limited to pharmaceutical drugs
ï· Toxicodynamics: what the xenobiotic/metabolic products do to the tissue
of the body -- that is, when the xenobiotic/metabolic byproducts react
with cell constituents, what changes to physiological function take place?
And how does this affect human health?
ï§ There is also pharmacodynamics
Risk and Exposure
ï· How is "risk" defined? Give an example which demonstrates the nuances of this
o Risk is the probability of injury or disease resulting from exposure to a potential
o The nuance is that the hazard itself is always seen as POTENTIAL, meaning that
a poison that is well secured is POTENTIALLY HAZARDOUS but not RISKY
because there is no way we will ever be exposed to it
ï· Talk about how our exposure to some substance is related to risk.
o It is very simple: the probable level of health risk is dependent on the
degree/likelihood of exposure because as demonstrated above, a substance is not
risky if there is NO chance we will ever bump into it
ï· A non-zero level of exposure is relevant when we CONTROL substances
instead of banning them (often done when they are useful)
o A complex issue related to the exposure-risk relationship is the notion of "no
exposure" -- does it mean no risk?
ï· In a way it does, but since a substance can still hang around in the
environment after it has been banned (especially if it is persistent), it is
very difficult to fully arrive at a "no exposure" state ï· Thus we have the concept of virtual elimination: the idea that we can try
our best to bans somethingâ¦we try to get rid of themâ¦but of course
there will always be a little bit left
ï· What are some sources of exposure to chemicals? Briefly discuss each.
o Environmental: air, water, food
o Occupational: hazards in the work place
o Therapeutic: things like drugs, medical device
o Diet: what is in our foods
ï· Note that therapeutic and dietary sources are getting increasingly mixed
up because there are lots of natural medications going on (i.e. herbal
products) these days
ï§ i.e. Nutraceuticals are also part of food now -- they are food in
nature but they have pharmaceutical properties
ï· i.e. Soy milk: high in certain types of hormone-like
substancesâ¦so people think that by taking soy milk,
they will maintain their hormone levels and avoid
Accidental: like if you have a large storage facility full of chemicalsâ¦and they
are accidentally released
o Deliberate: think Yushchenkoâ¦or also suicidal poisoning
ï· Explain what the concept of toxicity is.
o Toxicity is a function of the effectiDOSE (how much) of a xenobiotic AT its
target site, integrated over TIME (how long).
ï· As we see in the next question, the EFFECTIVE DOSE may not always
be the same as the amount of the thing which we take in
ï· What is the concept of internal exposure/dose?
o The idea is that when we absorb a xenobiotic into our bloodstream, that thing is
transformed by toxicokinetic processes such that the internal dose is quite
different than the external dose
ï· It is the cell or tissue that experiences the internal dose and so the ID is
actually the thing which is most directly relevant to our health
ï· Define route of exposure, give examples, and explain why we care.
o The route of exposure is essentially the SITE at which the toxin enters the body
o We care about this because:
ï· It is an important determinant of the ultimate dose -- that is, the
amount/rate of absorption from the external into the internal environment
is affected by the ROUTE through which it enters
ï· Also, in the case of a local toxic effect, the place where it enters will be
the place where the effect is seen
ï§ Note however that there are also SYSTEMIC responses, where
the effects are felt all over the body and not just locally
ï· Also it is notably that usually a given toxicant has a characteristic route
of exposure -- i.e. some drug gets into us the same way every time
ï§ However, sometimes toxicants can enter in more than one way --
i.e. something in water could be drank by us but we could also
absorb it dermally through the shower
o The sites/routes of exposure can include:
ï· Dermal (skin) -- although the skin is a barrier at times, it is also QUITE
thin and many substances can pass through the skin to varying
extentsâ¦get through the bloodstream and contaminate our bodiesâ¦ ï· Inhalation (lung) -- breathing/inhalingâ¦usually gas/vapor but also a dust
ï· Oral (GI) -- ultimately the small intestine in the GI tract
ï· Injection -- right into the bloodstream baby
Dose, Time, etc.
ï· What are the two time-related aspects of exposure which ultimately affect DOSE?
o The concept of DURATION: how long an organism is exposed to a chemical for
But also, FREQUENCY: whether we are exposed in a continuous mannerâ¦or if
it is more episodic (and of course, how often the episodes are, etc.)
ï· Also explain a time-related characteristic that has to do with a given substance's
NATURE (as opposed to dose).
o Here the idea we are referring to is acute exposure vs. chronic exposure
o Acute exposure is a single and time-limited exposure
ï· As a related