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toxins
natural chemicals that can cause adverse effects at low concentrations
toxicant
chemical synthesized by humans that can cause adverse effects at low concentrations (ex: pesticides, pharmaceuticals)
pollutant
a contaminant that causes adverse effects
contaminant
chemical not normally found in that environment
melittin
chemical found in bee venom that destroys cell membranes and causes action potential in nociceptors (pain receptors)
Hannibal Barca
military commander who had large pots and would throw venomous snakes at enemies
toxicology in the American Civil War
drop Clostridium botulinum bacteria into a well and anyone who drank from the contaminated well would die
Ebers Papyrus
first known medical records in history; first known books of poisons and some antidotes
toxicology in Ancient Greece
Socrates (philosopher) was thrown into prison and forced to eat hemlock as a form of execution
xenobiotic
A chemical substance foreign to the biological system
Catherine de Medici
queen of France; the first experimental toxicologist; she tested out her potions/poisons/remedies on the sick/poor
what did Catherine de Medici study? (toxicology)
- onset of action
- potency (effective-ness)
- site of action
- clinical signs and symptoms
Paracelsus
father of toxicology, said "the dose makes the poison"
Claude Bernard
used toxic substances to understand basic biological systems
ex: he used carbon monoxide to study oxygen binding to hemoglobin
toxicology
the study of adverse effects of chemicals and physical agents on biological systems
poisons
a substance that through its chemical action can injure or kill
descriptive toxicologist
concerned directly with toxicity testing in animals to evaluate the risk in humans
- mostly about pharmaceuticals and food additives
mechanistic toxicologist
concerned directly with trying to elucidate the toxin's mechanisms of action
Lake Apopka
1970s they found that the alligator population was decreasing; later found that DDT was an endocrine disruptor and mimics estrogen therefore decreasing populations of alligator were due to dumping DDT into lake
regulatory toxicologist
examines effects on non-target organisms/environment and makes regulations based on toxicology data
agencies involved with regulations
- Food and Drug Administration (FDA)
- Health Canada
- Environment and Climate Change Canada
- Department of Fisheries and Oceans (DFO)
clinical toxicologist
works in the realm of medical science, concerned with disease cause by or associated with chemical exposure
- main focus is treatments and antidotes
forensic toxicologist
mainly concerned with the medical and legal aspects such as determining cause of death in investigations, analytical chemistry and analyzing tissue
environmental toxicologist
study the effects of chemicals on the ecosystem and its components (wildlife)
priority pollutants list
list of chemicals where we need more information because there is a potential for them to cause problems to humans and the environment
CEPA Domestic Substances List
list of chemicals (inventory) of ~23,000 chemicals in Canada used commercially
- categorizes chemicals according to certain criteria
5 factors for selecting priority chemicals (categorization)
1. persistence
2. bioaccumulative
3. inherently toxic
4. quantity
5. other effects
3 main factors looked at by Canadian government to categorize priority chemicals
PBT
- persistence
- bioaccumulative
- toxicity (inherent)
diazinon
organophosphate pesticide used to control insects, inhibits acetylcholinesterase in nervous system
half life
length of time required for half of the radioactive atoms in a sample to decay
half life of DDT
2-15 years
transformation processes that degrade chemical over time
- physical (UV, temp)
- chemical (reaction)
- biological (microbes & fungi)
example of widespread contamination
DDT used for mosquito/malaria treatment in tropics but lots of DDT is found in the Arctic and Antarctic; accumulates in penguin fat cells
soil incineration
when soil is too contaminated to be re-mediated, it is sent to a special location to be incinerated (set on fire)
Stockholm Convention on Persistent Organic Pollutants
program run by UN; goal is to eliminate or resist POPs (persistent organic pollutants)
"the Dirty Dozen"
original list of 12 contaminants by the UN which has now expanded 16 more
chemicals in the "Dirty Dozen"
- DDT
- hexachlorobenzene
- endrin
- mirex
- aldrin
- polychlorinated benzene
- dibenzo-dioxins
- dibenzo-furans
example of different half-lives under different conditions
GLYPHOSATE
- breaks down well in tropics (hot, wet, increased amount of microbs) but poorly in Skeena (cold, wet, decreased amount of microbes)
bioaccumulation
the process by which organisms uptake foreign chemicals through all routes of chemical exposure (dietary, transport across respiratory surface, dermal absorption, inhalation)
bioconcentration
process by which a chemical concentration in an aquatic organism exceeds that in water as a result of exposure to a waterborne chemical (uptake only from abiotic environment)
biomagnification
accumulation of pollutants at successive levels of the food chain (uptake only from diet)
example of species dependent toxicity
ethylene glycol (antifreeze) toxic for cats not humans
common endpoint to determine toxicity
how much of chemical X does it take to kill something
- expose to varying concentrations of chemical and look at resulting mortality
LC50
Lethal Concentration 50%, the concentration which kills 50% of the tested animals
- affects mostly aquatic organisms because you don't know how much exactly got into the organism
LD50
the amount of a chemical that kills 50% of the animals in a test population
- you know exactly how much of the chemical got into the organism and thus killed them
other effects to take into consideration when classifying priority chemicals
- ability to influence atmospheric chemistry (acid rain)
- ozone (increase in freons)
- CO2 emissions
- odors (organosulfur compounds)
- foaming (detergents)
hydrophilic
water loving
hydrophobic
Water fearing ; sparingly soluble in water
lipophilic
Oil loving
- hydrophobic chemicals tend to dissolve in lipids
fugacity
tendency to flee (driving force for movement between two compartments)
K(ow)
octanol-water partition coefficient, determined by putting equal amounts of octanol and water in a container with compound X and measuring the concentration in each solvent after a period of time
low K(ow)
very polar (anything under 4)
high K(ow)
super hydrophobic/nonpolar
- characteristics of chemicals gets weird here
Bioconcentration Factor (BCF)
The concentration of a substance in biota divided by the concentration of the substance in surrounding WATER (Cf/Cw ==> concentration in fish over concentration in water)
bioaccumulation factor (BAF)
ratio of the concentration of a chemical in an organism to the concentration of the chemical in the surrounding environment
log K(ow)
used as a surrogate in determining if something is bioaccumulative
- log Kow > 5 = bioaccumulative
atmosphere solubility
chemical's tendency to partition to the atmosphere ; mostly controlled by vapour pressure
3 key chemical characteristics for examining environmental fate
1. hydrophobic or hydrophilic
2. "atmosphere solubility"
3. chemicals dissociation tendencies in an aqueous environment
point spill
significant amount entering environment at a single point in time & space; infrequent and contamination is very local
- ex: end of a pipe
non-point source
diffuse inputs on whole area/large time frames of agricultural releases
- difficult to control
widespread release
release of a substance in sufficient quantity and over a wide area
- measurable contamination of a part of Earth
horizontal atmospheric movement
atmospheric transport (Grasshopper event); mostly vapour phase
vertical atmospheric movement
deposition/particles moving up into the atmosphere
dry deposition
particles moving downward due to gravity (depending on atmospheric conditions)
wet deposition
acidic rain, fog, and snow (any precipitation)
- raindrops can pick up particles in atmosphere as it comes down
- vapour of chemical X can also partition into raindrop
surface water
Water above the surface of the land, including lakes, rivers, streams, ponds, floodwater, and runoff.
ground water
underground water that is held in the soil and in pervious rocks
advective transport
Water currents that move chemicals
diffusive transport
random motion of molecules
3 factors that affect surface water
1. pollution conditions
2. physical chemistry properties of pollutant
3. environmental conditions
log Koc
value that describes how well a chemical binds to organic carbon
types of processes in contaminant resuspension
1. physical
2. biological
types of physical processes
1. advection
2. diffusive
types of biological processes
1. microbenthic processes (microbial/mainly bacteria)
2. macrobenthic processes (organisms that live on the ocean floor)
how do microbenthic processes resuspend contaminant
- benthic microbes cause changes to sediment's chemistry (binding capacity, pH)
- bacteria enzymatically convert compounds from one form to another
- ebullition (sudden release of methane gas as bubbles)
how do macrobenthic processes resuspend contaminant
organisms in/on sediments burrow, hide, eating, etc
bioturbation
The process by which organisms rework existing sediments by burrowing
3 phases of toxic action paradigm
1. exposure phase
2. toxicokinetic phase
3. toxicodynamic phase
5 methods for passing membrane
1. filtration (channel protein assistance)
2. passive diffusion
3. active transport
4. facilitated diffusion
5. endocytosis
passive diffusion
movement of substances across a semipermeable membrane with the concentration gradient
- doesn't require energy
- most dangerous for hydrophobic chemicals
- first order process
important chemical characteristics for passive diffusion
- concentration/fugacity gradient
- lipid soluble
- non-ionized
Fick's Equation
rate of diffusion = [KA(C2-C1)]/d
- K = lipid solubility, size
- A = surface size
- C2-C1 = concentration gradient
- d = distance
factors for enhanced diffusion
high SA
high lipid solubility
high concentration gradient
low diffusion distance
active transport
the movement of materials through a cell membrane using energy
- zero order process (saturable)
facilitated diffusion
process of diffusion in which molecules pass across the membrane through cell membrane channels
- no energy required
- only occurs if there is higher [ ] outside than inside
endocytosis
- cell invagination enclosing particles in
- phagocytosis, pinocytosis and receptor-mediated endocytosis
sites of absorption/exposure
- skin
- gastrointestinal tract
- lungs
function of skin
to be a barrier (defense)
- 2 layers: epidermis (thinner. less blood more keratin) and dermis (thicker)
why lungs are good at gas exchange
- high surface area
- low diffusion distance
- high blood supply
perfusion-limited uptake
uptake of molecule depends on the amount of blood (low solubility in blood)
ventilation-limited uptake
uptake of molecule depends on the amount of chemical (high solubility in blood)
oxygen uptake in water breathers
- unidirectional flow of respiratory medium
- countercurrent exchange (blood moves in opposite direction than air intake)
ectotherm
an animal whose body temperature varies with the temperature of its surroundings
why GI tract is good at absorption
- high surface area
- low diffusion distance
- high blood supply
absorption in GIT affected by
- presence/absence of food in stomach
- gut microbiome
what can happen after absorption (4)
- storage
- biotransformation
- excretion
- action (target an organ for toxicity??)
blood is made of
plasma, white blood cells, red blood cells, proteins & lipids
- plasma = aqueous, everything else = organic
P-glycoprotein
a transporter protein that moves drugs out of cells and into the gut, urine, or bile
- uses ATP as energy
- large substrate base including xenobiotics
- able to grab xenobiotics from cytosol or between lipid bilayer
- multi-drug resistance (MDR)
- the ONLY method that kicks out hydrophobic chemicals
ivermectin & p-glycoprotein
- ivermectin is a neurotoxin used to treat parasites in dogs and other animals
- mutation in multi-drug resistance (MDR) could produce no p-glycoprotein & therefore ivermectin gets into brain of dog (fatal)
binding coefficients
the ability for chemical X to bind to tissue