Toxicology Flashcards
What is Toxicology, and what is a toxicant?
It is the study of toxic substances called Toxicants and then the study of the effects of these toxicants is called the study of poisons. A toxicant is a poisonous agent that produces an adverse biological effect.
What are toxins? and what is the study of toxins?
Toxins are toxicants that are produced by a living organism and the study of toxins is called Toxinology.
What is the difference between the term xenobiotic and anthropogenic? Provide an example.
Xenobiotic is a generalized term that means foreign substance to that organism which could lead to useful or toxic results (pharmaceuticals like Aspirin or metals like lead). In contrast, anthropogenic means caused or produced by humans, and is usually used to describe the origin of a substance that does not occur naturally like DDT.
Who is Paracelsus? What did he contribute
Paracelsus was the father of toxicology and he believed that the substance itself wasn’t toxic but the amount was. “All substances are poisons: there is none that isn’t a poison but the right dose does differentiate a poison from a remedy”.
The dose makes the poison.
What is Environmental Toxicology?
It is the study of the fate and effects of chemicals in the environment.
What are the classes of Environmental toxicants? Provide examples.
The classes of Environmental Toxicants are:
Radiation: Japan’s Fukushima Daiichi Nuclear Plant release, Atomic bombs dropped on Nagasaki and Hiroshima
Inorganics: metals, and ammonia/ammonium
Organics: Dioxins/Furans, Polycyclic aromatic hydrocarbons, Persistent Organic Pollutants (POPs), Persistent Bioaccumulative and Toxics (PBTs), Polychlorinated biphenyls (PCBs)
Pesticides: Insecticides, Herbicides, fungicides, rodenticides.
Complex effluents: STP effluent- , mine effluent, pulp and paper effluent.
What are some historically important toxic events discussed in this course?
There are 2 two historically important toxic events mentioned:
- The Chimney Sweep event- Percival Pott noticed that these Sweeps (chimney soot cleaners) had an increase in scrotal cancer and that it was due to the formation of polycyclic aromatic hydrocarbons produced from incomplete combustion.
- Mad Hatter event- Hat makers often worked with solutions containing Mercury and because of poor ventilation they inhaled these vapors leading to the accumulation of mercury and slowly poisoning the person (causing a neuropathology of them going insane hence the term (Mad as a Hatter).
What is the paradigm shift of environmental toxicology and its historical need for ecotoxicology.
During the Pre-industrial revolution (small rural-based communities), people thought the receiving environment could cope with the waste production- Dilution Paradigm (Over time it will dilute and go away).
But during the Post-industrialization (Big city formation), we realized that what you throw away can come back and hurt you like a boomerang - Boomerang Paradigm.
The importance of this is that we learned that we needed to understand and learn about the adverse effects of the waste products we release into the environment and how it can affect us in the future.
What are the elements of a toxic event?
- The production of a toxicant
- The release of the contaminant (toxicant becomes a contaminant when it is released into the environment)
- Movement of the contaminant to a receptor
- Exposure at a high enough contaminant level for a long amount of time (saturation)
- The response to that contaminant
What are the four routes of exposure for any organism?
- Diet
- Air
- Water
- Soil
What are the four routes of exposure for animals, the term used to describe the amount of toxicant they are being exposed to, and the specified units?
- Oral (mouth or diet) - Dose-> 1mg Kg-1 (1ppm)/ 1μg Kg-1 (1ppb)-> (weight of toxicant over the weight of organism)
- Injection (IV, SC, IP) - Dose -> 1mg Kg-1 (1ppm)/ 1μg Kg-1 (1ppb)
- Topical or Surface (Must enter the bloodstream) - Dose -> 1mg Kg-1 (1ppm)/ 1μg Kg-1 (1ppb)
- Respiratory (through lungs or gills) - Concentration -> 1mg L-1 (1ppm)/ 1μg L-1 (1ppb)-> (weight of toxicant over the volume of air/water)
What is a Bioassay?
Is a test to determine the strength of a toxicant on an organism in comparison to the standard population (Response). The test has 3 main components:
1. Test Organism
2. Exposure Time (how long)
3. Dose/Concentration (how much)
How are the toxicity responses classified?
There are two main classifications: the degree of the response and the timing of the response (each have subcategories)
Degree of Response-> Lethal (death) and sublethal (Individual, species, Community)
Timing of the Response-> Acute, Subacute, Chronic, Cumulative, Delayed.
What are classifications for toxicity response based on the degree of response?
It is Lethal- Death and Sublethal - doesn’t result in death
Lethal: a response that results in death.
Sublethal: Individual, Species. Community.
Individual changes: Biochemical ( Enzyme inhibition or induction), Hormonal (changes in cortisol levels due to stress or the VG issues in fatheaded minnow), Physiological ( changes in growth or reproduction),
Species: Changes in population structure.
Community: Changes in diversity and abundance of a species.
What are classifications for toxicity response based on the timing of the response?
Acute: What we observe is a severe stimulus that brings about a response within 96 hours (high Dose/Concentration) (Dose/[] is administered only once)
Subacute: What we observe is a stimulus between chronic and acute (could become chronic) (medium Dose/Concentration) (Dose/[] is administered only once)
Chronic: What we observe is a stimulus brings about a response slowly over a long period of time (over 10% of the organism’s lifespan) (low Dose/[]) (Dose/[] is administered only once)
Cumulative: What we observe is different or identical exposure results because the stimulus has been repeated several times. (multiple doses/[])
Delayed: Response does not emerge until well after the exposure to the stimulus, e.g., cancer.
What is a dose-response/toxicant-response curve and what are the most important parts of this graph?
It is a graph that shows the relationship between the dose/[] of a toxicant and the observed effects/response in the target/test organism
On the Y-axis-> You should have your endpoint (response)
On the X-axis-> Measured values (Dose/[] of a toxicant or Time)
We can specify either the time or the dose/[] and the opposite will be on the x-axis.
->For example, the effects (y-axis response) of different doses/[]s of a toxicant (x-axis measured value) after 96 hours.
->E.g., the effects (y-axis response) after a period of time (x-axis measured value) at a specified dose/[]
What are some different curves and their meanings?
If it’s flat: there is no effect in the exposure range
If it’s linear: There is no threshold (it is continuous)
If it’s flat and linear: show no effect until a certain threshold is reached, after which the response increases rapidly before leveling off at higher doses
If it’s J-shaped: It is often seen with hormesis (low doses reduce toxicity or possibly produce beneficial responses)
Why do we use Linear regression or look at 50 percent?
We use linear regression to see if our data is accurate and at 50 percent we have the closest 95% confidence interval (we are most confident) that’s why we use LC50, ED50, etc…
We look at Y-axis: Response probit (probability unit) vs X-axis: Log of Dose
What is an LC50?
It stands for Lethal Concentration 50% ( For the graph keep the time constant and vary the concentration):
Concentration causing lethality in 50% of the test organism in a given time.
What is LD50?
It stands for Lethal Dose 50% ( For the graph keep the time constant and vary the dose):
Dose causing lethality in 50% of the test organisms in a given time.
What is LT50?
It stands for Lethal Time 50% (For the graph keep the dose/[] constant and vary the time)
The time it takes for a specified dose/[] to cause lethality in 50% of the test organisms.
Can you report on non-lethal response and if so, how?
Yes, we can report on sublethal responses by looking at EC50, ED50, and ET50 dose curves. (E stands for Effective)
We can measure things like enzyme inhibition, inhibition of growth, metabolism, or an enzyme as a response.
What is EC50?
It stands for Effective Concentration 50% ( For the graph keep the time constant and vary the concentration):
Concentration causing a sublethal response in 50% of the test organism in a given time.
What is ED50?
It stands for Effective Dose 50% ( For the graph keep the time constant and vary the dose):
Dose causing sublethal response in 50% of the test organisms in a given time.
What is ET50?
It stands for Effective Time 50% (For the graph keep the dose/[] constant and vary the time)
The time it takes for a specified dose/[] to cause a sublethal response in 50% of the test organisms.
What are the key components of a toxicity test?
The key components of a toxicity test are:
- Find a Target Organism (in vivo) or Biomarker (in vitro- cell/ in vivo)
- Duration of the exposure
- Route of exposure
- Toxic endpoint or outcome
How would you design a toxicity test method?
My methods would be:
- Choose what the test organism/biomarker we want
- Reference a standardized toxicity test for the test organism/biomarker and a referenced toxicant.
- Choose the toxicant we want
- Set the duration for the test
- The route of the exposure which would help with the duration of the test
- Set a control and variations in doses/[]
- Multiple trials to account for variance
What is a standardized toxicity test and why do we use it?
Are test Bioassay that has been developed and has a standardized procedure that can be repeated the reason why we use it is because these procedures have been solidified (the data repeats no matter how many times we test it) and we can use it as a reference when measuring a similar test parameters.