Toxicology Midterm 2 Flashcards
Midterm
Describe some examples of algal toxins.
An example of an Algal toxin is Saxitoxin which is produced by dinoflagellate and contaminates mussels, clams, crabs and fish.
It causes a condition called Paralytic shellfish poisoning (PSP) which leads to the death of humans and seabirds.
Saitoxins inhibit electrical conduction in neurons by blocking voltage-gated sodium channels (Nerve impulse Suppression) impacting respiratory muscles and then leading to respiratory failure.
Explain what happens upon dermal exposure to sap from giant hogweed
Giant hogweed sap contains phototoxic compounds called furanocoumarins.
Furanocoumarins react with DNA when exposed to UV-A radiation (Abiotic Modifying factor) they form DNA adducts and damage them causing cellular death.
This causes burns, blistering and scarring.
What is the difference between a venomous animal and a poisonous one?
A venomous animal is one where it can produce a toxin actively for offensive purposes (They bite you), e.g. snakes/bees
A poisonous animal (Very bright colours and patterns to signify they mean business) is one where it acquires/accumulates poisonous metabolites/toxins from their environment they can’t produce it (You bite it), e.g. monarch butterflies/ poison dart frogs
What are the 4 main components of bee venom?
The 4 main components of bee venom are Melittin, Apamin, Mast Cell Degranulation Peptides and Hyaluronidase.
What is Melittin?
Melittin is a peptide with amphipathic properties that allow it to pass into membranes/phospholipid bilayers.
It forms pores in the cells that are either transient or stable.
What is Apamin?
Apamin is a small peptide that can cross the blood-brain barrier.
It affects the CNS
What are Mast Cell Degranulation Peptides?
MCDPs are peptides that react with Mast cells making them release histamines
They are also neurotoxic and inhibit Potassium channels.
What is Hyaluronidase?
Hyaluronidase is an enzyme that breaks down hyaluronic acid in tissues, this allows for other components of bee venom to spread through the tissue.
What are the elements of a toxicity event?
- The generation of contaminants (The name for a toxicant once released into the environment).
- Release of a contaminant to the environment.
- The Movement of the contaminant to a receptor.
- Exposure at a high enough contaminant level for a long enough amount of time.
- A response.
What is the difference between a point and a non-point source?
A point source is where the toxicant comes from a direct source (Can be traced) usual examples are industrial waste/ sewage discharge/ exhaust of the car.
A non-point source is where a toxicant comes from an indirect source (Hard to trace the exact source) usual examples are agriculture and urban runoff.
Describe what is meant by “accidental release”, “intentional release”, “deliberate application”, and “urban runoff” when describing contaminant sources.
Accidental release- Is the release of a contaminant through unforeseen circumstances e.g. nuclear accidents, oil spills, fires, and train crashes (Chernobyl/Fukushima Daiichi Nuclear plants incidents)
Intentional release- disposal or release of waste that is deliberate or routine can be non-point or point source (Sewage treatment plants P, Farms N-P)
Deliberate Application- Fertilizers or pesticides directly applied to the land (Leach into soil or groundwater).
Urban Runoff- Water that flows over cities that could carry contaminants into the environment (Not treated but first flush is very toxic).
Give some examples of how contaminants may enter the atmosphere.
Aerosols or gases are 2 examples of contaminants that enter the atmosphere.
Volatile Organic Compounds (VOCs) such as benzene or naphthalene can enter the atmosphere from either land or surface water.
Combustion (e.g., CO, CO2, NO, NO2, SO2, Metals hydrocarbons and particulates) and Incomplete Combustion (PAHs) allow compounds to be released into the atmosphere.
Incomplete combustion (PAHs) allows compounds to be released into the atmosphere, these compounds are highly problematic.
Give some examples of how contaminants may enter land and groundwater.
Landfills are used to deposit domestic and industrial waste and contaminants allowing them to leach into (L/GW)
Some are released intentionally like pesticides, fertilizers, manure, sewage sludge
Combustion produces particulates and volatiles which adsorb (toxicants stick to the surface of an organism)
Storage tanks can leak and expose the environment to contaminants.
What is water solubility?
Is the maximum amount of substance that can dissolve in water at Eq (hydrophilic contaminant)
What is KOW how is it measured and what do those values mean?
KOW/ log10KOW (If the value is too high) is the octanol-water coefficient and is used to measure hydrophobicity (how lipophilic it is).
The test is conducted by adding a toxicant to equal parts octanol and water and then measuring the [] of that toxicant dissolved in each solvent.
KOW= [] of chemical in octanol (Represents all biological lipids)/ [] of chemical in water.
Low KOW = Hydrophilic (Lipophobic)
High KOW= lipophilic (Hydrophobic).
This helps us to determine the fate of the toxicant and how it interacts with the body.
What is the Henry’s law coefficient? What is the equation?
Is the ratio of vapour pressure to the water solubility.
It describes the partitioning between a liquid and a gas (KAW/H).
H(KAW)= [] of chemical in air/ [] of chemical in water.
Low H- Higher Water solubility
High H- tends to escape from water and enter the atmosphere (e.g. naphthalene)
The purpose of this equation is to tell us where the toxicant ends up if found in water, does it stay in the water or end up in the atmosphere (Air vs. water phases)
What impacts environmental half-life?
The presence of double bonds or oxygen function groups makes organic compounds more susceptible to attack.
Enzymes and light break down the contaminant making it less persistent.
The replacement of hydrogen by halogens makes the contaminant highly resistant to degradation making them highly persistent (PCBs, Dioxins/Furans)
What processes contribute to the loss of contaminants in the environment?
Hydrolysis, Oxidation, Photolysis, radioactive decay- Sometimes these processes may produce more toxic compounds (e.g. paraquat->photolysis).
Complexation (forming complexes with other chemicals), buried in sediment - Changing conditions or physical disturbance (Anthropogenic release typically) may lead to re-mobilization.
Dilution in the ocean or atmosphere gives us an aspect of reduction.
Describe some examples of environmental factors that may impact the loss of contaminants in the environment.
- Temperature, Light, Redox potential, pH
- Ionic composition of water (Water Hardness)
- Microbial activity and substrates of the activity (Biomethylation)
- Dissolved organic carbons (DOC)
- Sedimentation rates
What is the fate of inorganic pollutants?
Inorganic pollutants forever persists because they contain metals, since metals are elements they cannot be destroyed.
The ultimate environmental sink is the ocean- inorganic pollutants will wither be deposited into sediment or stay in solution.
The only time we see a breakdown of an inorganic pollutant is when we deal with radioisotopes because they undergo radioactive decay.
What is bioavailability?
It is the extent to which a contaminant in a source is free for uptake
What factors influence the bioavailability of inorganics in water phases versus solid phases?
For inorganics in water:
pH- An example would be ammonia vs ammonium
Chemical speciation- When in water do these metals/metalloids bind with ligands ((Dissolved organic compounds (Humic/Fluvic acid), complexation with carboxylic groups))
Competing cations- Ca2+, Mg2+, Cu2+, Cd2+, Zn2+, Co2+
Free metal ions (more toxic) are more bioavailable than their complexed counterparts (less toxic), we can understand how free metal ions interact with the Free-Ion Activity Model (FIAM)
What factors influence the bioavailability of organics in water versus solid phases?
Bioavailability of organics can depend on its source:
In water they can be described with structure-activity relationships (SAR), use molecular qualities of organics to predict activity (e.g. Poly Aromatic Hydrocarbons, they all contain benzene rings) if expressed quantitatively (QSARS- molecular weight, surface area, or charge distribution)
In their solid phase there are 2 ways of uptake:
Inhalation- It is able to be up taken into the body due to particle size: larger particles get removed by the nose hairs, 5-10 um is able to reach the pharynx, 1 um particles can even reach terminal bronchi & alveoli
Ingestion- They can be up taken by the body eating them, e.g., small children eating paint chips containing lead, lead shot ingested by birds are processed and slowly release lead into the system (makes them lose wing structure)
Describe the influence of pH on ammonia/ammonium bioavailability.
When the pH shifts NH3 becomes NH4+, NH3 can readily pass across cell membranes where as NH4+ can not.
Ammonia has an increased bioavailability in its unionized (NH3), and decreased bioavailability when its ionized (NH4+)
Describe how metal toxicity can change due to water hardness.
Water hardness changes metal toxicity due to the [] of divalent cations, the higher [] of essential metals in water lowers the bioavailability of metal toxicants because they compete for absorption.
-E.g. Ca2+, Mg2+, Cu2+, Cd2+, Zn2+, Co2+
What is the biotic ligand model?
Is the mechanistic approach to determine bioavailability incorporating water chemistry and metal speciation.
This model has been developed from the Free-Ion Activity Model (FIAM) & Gill Surface Interaction Model (GSIM)
The practical use of this is to understand the competition of free metal ions with other naturally occurring cations for metal binding sites (Ca, Na, Mg)
How do free metal ions compete with naturally
occurring cations for metal binding sites?
The reason why free metal ions compete with naturally occurring cations is because of their charges.
When we look at Na1+ transporters we notice that the metals that compete are Ag1+ & Cu1+, since the charges are similar they can be up taken by these pathways
When we look at Ca2+ transporters we know that the metals that compete are Zn2+, Cd2+, Pb2+, Co2+, Cu2+
What is a structure-activity relationship (SAR)?
Structure-activity relationships (SAR), use molecular qualities of organics to predict activity (e.g. Poly Aromatic Hydrocarbons, they all contain benzene rings) if expressed quantitatively (QSARS- molecular weight, surface area, or charge distribution)
How does KOW impact the bioavailability of organics in solid phases?
In the environment and food KOW influences the bioavailability of lipophilic contaminants:
For very large and hydrophobic compounds the uptake of these compounds are low.
PCBs with high KOWs (hydrophobic) adsorb into the soil but are not available for uptake by plants.
Many pesticides have low KOWs (hydrophilic) allowing them to be taken up more easily by plants.
How does a toxicant bioaccumulation or bioconcentration?
Remember ABDE:
A. Absorption/Uptake of the toxicant
B. Role of Biotransformation
D. Is the toxicant Detoxified?
E. Is the toxicant Eliminated & how or does it accumulate?
What is bioaccumulation or bioconcentration?
Bioaccumulation is the net accumulation of a contaminant in/on an organism from all environmental sources
Sources: Air, Water, Soils/Sediments, Food/Trophic transfer.
Bioconcentration is the net accumulation of a contaminant in/on an organism from water (Aquatic Toxicity), and we can use the BCF to determine the fate of this contaminant.
When looking at the Accumulation graph understand Accumulation phase, depuration phase, when it’s moved into a clean environment, whether it’s persistent or leaves the organism (BCF graph is slightly different)
How is BCF determined?
BCF is determined in a steady state (highly monitored conditions), and it tells us the fate of the toxicant in the organism.
It is calculated by [] of the toxicant in the tissue (mgKg-1)/ [] of toxicant in water (mgL-1)
When looking at the BCF Graphs (Accumulation graph for Bioconcentration) the end point is the will tell you whether or not it has a Low or high BCF
What are the factors that influence bioaccumulation?
Chemical Properties of the Substance:
Lipophilicity
Persistence
Water Solubility
Organism-Specific Factors:
Metabolism
Life Stage and Size
Feeding Habits
Sex- female mammals are able to excrete through lactation (milk has very high fat content), males have no mechanism.
Environmental Conditions:
Temperature
pH
Water hardness
Exposure Pathways:
Dietary Intake
Direct Uptake from Environment
Why do some chemicals
bioconcentrate?
Some chemicals bioconcentrate due to their high BCF which means that the more lipophilic the contaminant the longer it stays in the body and accumulates.
What is the impact of lipophilicity on BCF?
BCF and lipophilicity can be related:
The more lipophilic the contaminant is more it accumulates in the body, it is very persistent but there is a threshold for how much chemical the fat tissue can hold. If its Hydrophilic it’s usually easier to excrete.
High KOW-> High BCF (e.g., Dioxins and PCBs), there are solubility limits (amount of chemical fat tissue can hold)
Low KOW-> Low BCF easier to excrete since hydrophilic or attracted to water (e.g., metals), the only time complications occur is when there are pumps or channels involved
What are other factors that can influence
bioconcentration?
Lipid concentration and composition of the organism, the higher the concentration the more it will accumulate (seals, walruses), the composition of the fat tissue might make it more susceptible to certain chemical.
The weight of the organism, it is implied that the more mass an organism has the more it can bioaccumulate/concentrate. Surface ratio is also important smaller species exchange with surrounding aqueous phase faster than larger organisms.
The uptake route is also important- An organism can take up a contaminate either from direct exposure from the water or through digestion
Metabolic Activity- increased metabolism may result in an increase in excretion of the chemical.
What is biomagnification?
Is the increase of concentration of a chemical as one moves up the food chain (trophic levels).
A chemical must bioconcentrate and persist in the body (body burden), when the animal is then consumed by a predator it then builds up in their bodies because they are able to contain high [] of the chemical, the higher the animal is on the trophic level the contaminant will have a higher burden than their prey.
What is an example of biomagnification as discussed in this
course?
An example is bird eating fish because of the release of DDT in the ocean and the build up of the contaminant from each level of trophic level.
DDT effects calcium-dependent ATPase in the shell glands of these birds and their eggs would be extremely brittle and won’t survive.
What are the basic parts of toxicokinetics?
A. Absorption/uptake of a chemical that enters the body
D. Distribution of the chemical from the entry site to other sites in the body
B. Biotransformation of the chemical from one form to another (metabolites)
E. Excretion/elimination of the chemical or metabolite from the body
What are the three routes of uptake of toxicants and factors that lead to its uptake.
The speed of transport and path is highly dependent on water solubility, lipophilicity (KOW) and molecular size.
The main locations of exposure are gills, lungs, guts, and skin/surface.
The 3 routes of uptake are:
1. lipid
2. Aqueous
3. Endocytic
What is the lipid route?
Lipophilic contaminants through the lipid bilayer of the membrane, substances with high lipophilicity can readily diffuse across the lipid bilayer and plasma membrane, passive diffusion is the movement of a chemical down its concentration gradient.
Remember diagram
What is the Aqueous route?
For the aqueous route is via membrane transport proteins (channel/carrier proteins), hydrophilic contaminants transfer into the cell easily through non-specific channels (porins), some are specific like Ca dependent channels and Cd that compete with it.
Remember diagram.
What is the endocytic route?
Metals that bind to a proteins on the surface of the cell are then engulfed and incorporated into a vesicle which fuses with a lysosome thus releasing the metal into the cell.
Remember diagram.
In a large organism, how are lipophilic versus hydrophilic toxicants distributed in the
circulatory system?
Toxicants travel through the circulatory system by blood
lipophilic toxicants bind to the blood cells.
Hydrophilic toxicants bind to plasma.
What is the path that blood takes from the digestive system (gut) in vertebrates?
All the blood leaving the gut travels to the liver allowing hepatocytes (power house of xenobiotic metabolism) biotransforms the toxicant for elimination.
In vertebrates what happens to toxicants that are absorbed into the blood?
Once it is biotransformed toxicant may travel to the liver -> kidney -> adipose tissue -> bones
What is biotransformation?
Biotransformation is a metabolic process where the parent toxicant is transformed into a metabolite to help it be excrete/eliminated by the organism.
What are the possible outcomes of the subsequent compound
after biotransformation?
The purpose of biotransformation is to convert lipophilic compounds into a more hydrophilic compound so it can be eliminated, the outcomes can differ:
the metabolite can become non-toxic or it can be activated and become even more toxic (e.g., parathion converts to paraoxon becoming a very lethal compound)
What are the outcomes of biotransformation for inorganics?
Since metals can’t be destroyed so they are either sequestered (hides the inorganic) or removed from the organism
Describe the biotransformation process for metals in microbes.
Microbes transform metals by adding ethyl or methyl groups to deal with the toxic effects of the metals this is called biomethylation.
E.g. Sulfur reducing microbes methylate Hg sequestering it created Methyl Mercury
Describe the biotransformation process for metals in plants.
Plant cells can also biomethylate metals to reduce toxicity like As -> monomethylarsonic acid.
Higher plant cells sequester or eliminate metals by producing metal-binding proteins called phytochelatins (similar to metallothionein-like protein in vertebrates)
The presence of Cd, Cu, Hg, Pb, Zn upregulates gene expression for the genes that code for phytochelatins
Describe the biotransformation process for metals in invertebrates.
Invertebrates may sequester metals and other cations through a process called biomineralization (e.g., an example would be like how insects and molluscans incorporate Pb into their exoskeleton) they either shed their exoskeleton or retain these shells that renders the metal unavailable to have an impact on the organism
Describe the biotransformation process for metals in vertebrates.
Vertebrates sequester metals with the use of proteins called metallothionein’s (reduces the availability of metal)
Metallothionein’s are small sulfur-rich proteins that contain 25-30% of an amino acid called cysteine (contains sulfur), they can bind 6 or 7 metal atoms per molecule.
Production of this protein is induced by metals like Cu, Zn.
Metallothionein’s genes are activated when metals bind to metal-responsive transcription factor 1 (MTF-1) which then bind to metallothionein promoter and induces expression of the metallothionein.
Describe phase I in xenobiotic metabolic pathways.
Phase I- Is the first step of biotransformation when an organism wants to deal with an organic toxicant is the enzyme attacks the compound causing oxidation, hydrolysis and reduction reactions.
Most phase I enzymes are Cytochrome P450’s (CYPs) or a Mixed Function Oxygenases enzymes (MFOs), some times metabolites may become less toxic or more toxic (e.g., epoxide formation)
Invertebrates have rudimentary or no CYP enzymes
The most potent inducer of CYP is TCDD due to its size and planarity of its ring structure, PAHs/PCBs also induce CYP.
Dioxins & PCBs induce CYP1A
By isolating microsomes we can find CYP through homogenization.
CYP contains a heme group that binds to O2, CO2, CO.
Describe phase II in xenobiotic metabolic pathways.
Phase II enzymes conjugate endogenous compounds to make phase I metabolites even more water soluble, once conjugated they could become inactive.
Glucuronide -> glucuronyl transferase
Glutathione -> glutathione-s-transferase
Sulphate -> sulfotransferases
Amino acid conjugation
It then goes to the kidney for excretion.
Describe the biotransformation pathway for Naphthalene.
Phase I:
- Oxidation (naphthalene epoxide)
- Hydrolysis (naphthalene 1,2-diol)
Phase II:
3.Conjugation of naphthalene 1,2-diol with glucuronic acid
4. Allows for increased water solubility and subsequent elimination
Naphthalene is successfully sequestered without increased toxicity
Describe the biotransformation pathway for B[a]p
Phase I:
- Oxidation (B[a]P-7,8-dihydrodiol-9,10-epoxide) - forms a potent carcinogen
Phase II:
- Conjugated with an amino group (Extremely potent carcinogen)
Mutations will occur, some times the body catches it, or mutations are not caught and cause cancer
How are toxicants eliminated in vertebrates?
Major routes of excretion in animals are:
Primary sites- Urine, feces, and bile
Secondary sites- lungs/gills
Other minor sources are breast milk, sweat, saliva, hair, and skin
What are examples of elimination routes for plants?
Plants eliminate toxicants by leaching, evaporation from surfaces, leaf falls
What are examples of elimination routes for invertebrates?
Invertebrates such as arthropods can eliminate metal contamination via exoskeleton moulting (shedding)
What is animal cell culture?
An animal cell culture allows us to evaluate cellular toxic effects and molecular changes without using an entire organism and we grow these cells in vitro.
We are for mechanisms of cell death and accessing the viability of cells after toxicant exposure.
Ross Harrison first developed the cell culture technique, used frog nerve cells grown in lymph clot using the hanging drop method.
Describe the details of the four main requirements to
culture animal cells.
- Sterile environment to manipulate culture (culture hoods)
- Proper culture environment to support cell growth (Incubator)
- Nutrient environment to support cell growth (Medium= Antibiotics+ serum)
- Appropriate physical support (needs attach to surface of viable )
Types of cell cultures.
Animal cells are isolated from the tissues using mechanical or enzymatic protocols.
- Comes the primary culture (derived from initial tissue)
- Then its placed in a cell line
There are 2 types of cell lines:
- Finite cell line- A cell line that has a limited number of divisions
- Continuous/immortalized cell line- A cell line that has an indefinite lifespan due to immortal cells.
What did Rudolf Virchow (The father of modern pathology) say?
“Whole organism does not get sick-but only certain cells or group of cells”
What are the two main mechanisms of cell death?
Apoptosis:
1. Is a carefully regulated energy-dependent process of cell death
2. It is programmed cell death “cell suicide”
3. DNA is cleaved (180 bp fragments)
4. Blebbing of cell membrane
5. Might be caused by depletion of nutrients
Necrosis:
1. Unprogrammed cell death
2. No characteristic changes as seen in apoptosis (DNA cleavage, blebbing)
3. Plasma membrane is disrupted- cellular contents expelled into extracellular environment
4. Caused by sudden severe stress
Describe each of the different cell viability assays.
Cell membrane integrity- Dye exclusion & Retention assays
Metabolic activity- MTT & Resazurin assays
Lysosomal activity- NR dye assay
What is the difference between a dye exclusion assay versus a dye retention assay?
The major difference is that a dye exclusion assay stains dead cells blue, where a retention assay uses a dye that penetrates the cell and then becomes fluorescent.
Dye Exclusion- Trypan blue is a dye they use to stain dead cells and identify them, trypan blue is is a bulky chemical and viable cells won’t allow it enter cell (Measure of dead cells)
Retention assay- They add CFDA a non-polar, non-florescent dye to cells that rapidly diffuses into cell and then is converted by non-specific esterase’s of living cells to CF a polar fluorescent chemical (Measure of viable cells).
What is the difference between the MTT and the resazurin assays? What does each measure?
MTT assay measures mitochondrial activity through oxidative metabolism, the dye is reduced by succinate dehydrogenase, yellow dye will turn blue when reduced, sometimes there isn’t enough succinate dehydrogenase to get a response from the MTT assay.
Resazurin assays- measures both mitochondrial and cellular metabolic activity, through the reduction of resazurin by diaphorase enzyme in cell and mitochondria, will turn purple/pink when reduced.
What is the lysosomal activity assay?
Neutral Red (NR) is a dye that is used in cell staining determine cell viability, viable and uninjured cells take up NR into the lysosomes, dead cells don’t have this ability.
What molecules do class A versus class B metals associate with?
Class A metals (ligands) are associated with targeting molecules such as phospholipids and nucleic acids
Class B metal (ligands) are associated with targeting amino acids and proteins
Required: Fe, Ca, Zn, Na, K
Trace nutrients: Se, Cu, Co, Mg, Mn
Non-metabolic: Pb, Cd, Ni, Sn, Hg, Ag
Describe the toxicity of Lead. What are the targets?
Lead is a ubiquitous toxic metal with multiple routes of exposure: air, water, and food. (ceramic containers with lead glaze, fuel additives, lead-based paints, lead pluming pipes)
Inorganic lead is absorbed through the GI tract, skin, and respiratory tract and can be found in blood, liver, kidney and bone tissue with prolonged exposure.
Pb targets the hematopoietic system and impacts haeme synthesis, it inhibits the production of ALAD and HS through the mechanism of displacing zinc which is essential to the activity of ALAD.
Symptoms include: impacting the development of the nervous system, ataxia, stupor, coma, and convulsions.
Describe the toxicity of inorganic mercury and organic mercury.
Inorganic Hg (Metallic/Inorganic) doesn’t bioaccumulate because it is not readily assimilated into the body
Organic Hg (MeHg) is readily absorbed by organisms it is highly toxic and bioaccumulates
Methyl Hg can easily pass through the blood brain barrier as it forms a complex with cystine in blood plasma becoming structurally similar to methionine and gains passage through methionine carrier proteins- interferes with protein synthesis and neurotransmitter production.
What is the role of biomagnification in mercury toxicity
Hg’s organic form is where biomagnification occurs with its organic form, both inorganic and organic Hg is primarily excreted via bile (feces) but some reuptake occurs in the gut, most of the body burden is the muscle unlike other POPs who associate it with fatty tissue.
Biomagnification occurs through trophic levels and can even reach levels of contamination where they are unsuitable for even occasional consumption
What are some examples of mercury toxicity as discussed in this course?
In Japan Chisso Corp dumped larger discharge of Hg waste into Minamata Bay which lead to the consumption of contaminated fish normally found in the diet of the people in the area
Poisoned thousands of people they called Minamata disease.
Dryden, Ontario- The Dryden chemical company pulp and paper mill generated Hg waste and dumped effluent into English-Wabigoon River, this caused Minamata disease but no official diagnosis was made, health advisory still in effect after 60 years.
Describe the toxicity of other metals such as cadmium
Cd has been known to cause acute toxicity in humans symptoms are: nausea, vomiting, abdominal pain (ingested), pulmonary edema (inhalation)
Cd chronic toxicity impacts the kidneys
In Japan Cd toxicity occurred due to the use of contaminated river water for rice irrigation, Cd replaced Ca in bones and caused severe pain in joints and brittle bones (itah-itah: Japanese for it hurts it hurts)
Tobacco plants love to accumulate Cd and this could be a route of exposure for people who smoke, it gets deposited in lung tissue and absorbed into blood circulation
How is ammonia toxic to fish?
Ammonia expresses itself as a neurological disorder, and it can substitute K at nerve membrane-> compromising nervous system function
We can physically see this when the fish have a loss of eq(can’t swim), convulsions and death
How does ammonia move across the fish gill?
- NH3 freely diffuses into the membrane/ NH4+ doesn’t
2.If there is a pH change and NH3 becomes ionized NH4+ (similar hydrated radius as K+) the organism will have to expel NH4+ through Na+ active transport and use ATP to do so
What factors influence the toxicity of ammonia?
pH and temperature influence the toxicity of ammonia, but mostly pH (abiotic modifying factors)
When there is a pH shift and it keeps/converts ammonia in its unionized form, as we already know NH3 has an increased bioavailability compared to its ionized form NH4+
What is the Stockholm Convention? What are the three annexes with regard to targeting POPs?
The Stockholm Convention is an international agreement to limit the use of persistent and Bioaccumulative chemicals.
Annex A: List of chemicals that need to be eliminated
Annex B: List of chemicals with restricted use
Annex C: Unintentional production
What are some examples of the toxic effects of PAHs?
When metabolized PAHs can form reactive metabolites (epoxides) they bind to cellular proteins and DNA- it leads to mutations, developmental malformation and cancer.
PAHs may be activated in the liver and undergo AhR-dependant/induction in the lungs they can form DNA adducts, protein adducts or oxidize macromolecules in cells (lead to cancer)
E.g. B[a]P transformed in vivo to BP-7,8-epoxide -> further metabolized into BP-7,8dihydrodiol -> then metabolized to BPDE which reacts with DNA
- Leads to a mutation on the p35 gene which leads to carcinogenesis linked to human lung cancer
What are some examples of the toxic effects of Hexachlorobenzene?
The consumption of bread made from HCB fungicide-treated grain.
3000 people developed porphyria cutanea tarda and mixed porphyria
Hypertrichosis, porphyrinuria, and blisters when exposed to the sun.
In mammalian studies the oral LD50 are extremely high, chronic exposure can cause hepatomegaly, alopecia, ataxia, and liver/thyroid tumours.
What are some examples of the toxic effects of dioxins?
Dioxins induce MFOs, acute toxicity can range.
TCDD toxicity is mediated by ArR-signalling
They examined the effects of 2,3,7,8-TCDD in fathead minnow, channel catfish, lake herring, medaka, white sucker, northern pike, and zebrafish.
They noticed that it caused “blue sac” toxicity in fish larvae (death)
We see Cranial edema, jaw and heart malfunctions, Yolk sac edema
What are some examples of the toxic effects of paraquat?
It is biologically unavailable but adsorbs through soil/sediment, almost all poisonings are from ingestion (non-volatile & hydrophilic)
In aquatic organisms- paraquat is more toxic in soft water and in the early developmental stages of some fauna, such as certain crustacean species and frog tadpoles.
In birds- they exhibit excessive drinking, regurgitation, imbalance, muscular incoordination, terminal convulsions
In mammals- exhibits time-dependent accumulation in the kidney and lungs. Carrier-mediated transport of paraquat into the cells (it undergoes redox cycling and the production of superoxide) Produces other ROS (mainly H2O2)
Phase I- Destructive phase: Alveolar type I & II epithelial cells are destroyed
Phase II- Proliferative phase: Extensive fibrosis in the lungs (dyspnea, cyanosis, respiratory failure).
What are some examples of the toxic effects of MPTP and its symptoms?
MPTP is a contaminant produced from the synthesis of MPPP.
MPTP crosses the blood-brain barrier and gets metabolized by MAOB by the glial cells of the brain and produces MPP+
MPP+ is taken up by dopamine transporters in the brain, it inhibits the electron transport chain resulting in oxidative stress in dopaminergic neurons and 3 days developed symptoms of Parkinson’s disease (tremor, hypokinesia, and rigidity)
What is an effluent? What would make it a “complex effluent”?
Effluent is a waste product formed after domestic and industrial processes.
Complex effluent is when multiple compounds are added to the mix giving it a complex composition making it hard to treat. (could end up beneficial or detrimental)
What is the difference between additive, synergism, and antagonist with regards to toxicant mixture exposure?
Antagonistic- This is when the compounds interfere with one another
Additive- Is when the compounds have a combined effect
Synergism- This is when the compounds have a greater effect than when acting alone.
What is BKME and why is it important?
BKME is bleached kraft mill effluent is a very complex mix of hundreds of different compounds, and it is important to understand how they all interact with each other and the environment.
Describe the different toxicants that could be found in pulp and paper mill effluent.
3 main toxicants of focus in pulp and paper mills is:
Resin acids- E.g., dehydroabietic acid (DHAA) is a class of acids that are the deadliest chemicals in pulp mill effluents to fish (large amounts and persistent in environment)
Dioxins & furans- TCDD
Chlorinated phenolic compounds: 2,4,5-trichlorophenol
Describe the induction of CYP upon exposure to dioxin.
The aryl hydrocarbon receptor (AhR) is activated (binds)when an AhR-inducing agent is present (Dioxin), it will then be allowed into the nucleus with the help of AhR nuclear translocator, they then bind with the dioxin response element and promote the transcription of the CYP1A1 mRNA then carries a code that determine the composition of amino acids that code for the CYP450 enzyme and then the activity can be measured with EROD assay.
Label the diagram of a
hepatocyte exposed to TCDD
Memorize graph
