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.
