3 bioaccumulation & toxicokinetics Flashcards
what is toxicokinetics?
ADME: what organisms do to the toxicant
-absorption/uptake processes
-internal handling and metabolism
-excretion
what is the graph of the simplified conceptualization of bioaccumulation?
is bioaccumulation a dynamic or static process?
highly dynamic process
-depends on the physiochemical properties of toxicants
what are some important aspects of bioaccumulation?
-growth dilution
-bioconcentration
-biomagnification
what is growth dilution?
the concentration of a contaminant (ppm or ppb) can decrease in a growing organism; it is not a component of elimination though
-rate of tissue growth is higher than uptake
-not a universal phenomenon, only see for necessary elements (iron, copper)
-mostly see in tropical or temperate climates, not in cold (slow tissue growth)
-no net increase in bioaccumulation
what is bioconcentration?
-defined as the uptake of dissolved phase of a toxicant to achieve total body concentrations that exceed the dissolved phase of water
-term limited to use in aquatic toxicology
-contaminants are more concentrated in organisms tissue than in water
what is the example of the bioconcentration of mercury (ppm)?
what is the graph of the biomagnification of DDT?
when you increase trophic level, the concentration of toxicants increase by 10-fold
what is the graph of the biomagnification of mercury in the arctic?
what is biomagnification?
-defined as the increasing concentration of a toxicant from lower to higher trophic level (up the food chain)
-note: not all contaminants, but some selective contaminants undergo magnification
what are the differences between naphthalene and DDT?
DDT
-biomagnifies
-chlorinated hydrocarbon (very persistent)
-retained in the body for a long time (lipophilic)
naphthalene
-doesn’t biomagnify
-no chlorine
-enzymes can easily break it down
-doesn’t stay in body
what are the differences between copper and mercury/cadmium?
copper
-doesn’t biomagnify
-essential element (natural to the body)
-able to maintain homeostasis (eliminate when needed)
mercury/cadmium
-does biomagnify
-foreign elements (non-essential)
-difficult to get rid of
-10 years to eliminate 1 molecule of Hg
-high affinities for sulfur (bind so tight so retained in body
what are the three phases of toxic action?
- exposure
- toxicokinetics
- toxicodynamics
what is the exposure phase of toxic action?
BIOAVAILABILITY
-physical factors (of toxicant and/or environment)
-chemical factors (of toxicant and/or environment)
-biological factors (physiology, age, behavior, etc)
what is the toxicokinetic phase of toxic action?
what body does to the toxicant (partitioning)
-absorption
-distribution
-metabolism
-excretion
what is the toxicodynamic phase of toxic action?
what toxicant does to the body (potency)
-effects at site of toxic actions
-toxicant specific sensitivity
-intra- and inter- species variability in response
what are lipophilic molecules?
not water-soluble
-typically non polar (neutral charge)
what are hydrophilic molecules?
more water-soluble
-polar and typically electrically charged
__________ is most common mechanism of absorption or uptake
DIFFUSION
which molecules use simple diffusion across a cell membrane?
lipophilic compounds (nonpolar, neutral)
-must have a concentration gradient (high to low)
what molecules can use diffusion through channel, like a gated ion channel?
free ion metals (Cd2+, Pb2+) (cations)
-only form where metals can pass through membrane is in their free ionic form
-calcium analogs can mimic calcium and therefore use calcium channels (gated or not)
-does also need electrochemical gradient (cytoplasm is usually negative, so it drives transport)
-Cu+ and Ag+ are sodium analogs and therefore can use sodium channels
what molecules can use facilitated diffusion?
metalloids (e.g. AsO3-, SeO32-)
-polar, charged anions
-need transported, but still follow electrochemical gradients
which molecules can use paracellular pathway diffusion?
go between gap junctions
-pressure gradients
-if very small molecules
what is another major uptake pathway (that isn’t diffusion)?
active transport (e.g. Cu+, Ag+)
-most abundant is Na/K pump
-energy driven process (need ATP because its an ion pump)
-pump against concentration gradient
what is uptake via endocytosis?
-for large molecules (ones that can’t fit for diffusion)
-outside: infolding of cell membrane
-inside: release of molecules
-example: ultrafine particle uptake by lung epithelial cells
what is distribution (partitioning)?
where toxicant goes depends on chemical properties (for storage)
-lipophilic site is adipose tissues (fats)
-metals will accumulate in bones (calcium analogs)
-strong affinity for sulfur will go to the kidneys?
-organic form of mercury (MeHg) can cross BBB because it is a very small particle. Therefore and target brain and CNS making it a neurotoxin
what is the distribution/metabolism of trace elements in the bloodstream?
metal detoxification process which is a finite process (can get saturated)
-plasma has a lot of carrier proteins (transport proteins): albumin, ferritin, transferrin, ceruloplasmin
-transport of metals occurs through plasma carrier proteins which bind to molecule and then delivery to target
-in free ion form, metals are very reactive (very damaging) which is why we need detox systems (MT=metallothionein, GST=glutathione, MRG=metal rich granules)
what is the metabolism of toxicants?
-these phases are highly evolutionary conserved
-lipoproteins and triglycerides are carriers for lipophilic molecules to target
-body needs to detoxify and make water-soluble
-lipophilic are harder to get rid of
-hydrophilic is easier because they can be easily excreted and can already be water soluble
-we have endogenous lipophilic molecules, such as steroid hormones, which also need to be biotransformed and excreted
what is an example of biotransformation?
Naphthalene
-lipophilic, PAH (polycylic aromatic hydrocarbon)
what is excretion?
major routes for excretion are: bile, feces, urine, lungs/gills
-urine is by far the most important, followed by feces and bile
-lungs are important for the excretion of volatiles (e.g. alcohols, solvents)
what is the graph of the summary of toxicokinetics?
