Podcast
Questions and Answers
What does the concept of LOAEL stand for?
What does the concept of LOAEL stand for?
What is the primary purpose of establishing an Acceptable Daily Intake (ADI) for a substance?
What is the primary purpose of establishing an Acceptable Daily Intake (ADI) for a substance?
What is the role of the Safety Factor (SF) in calculating the ADI?
What is the role of the Safety Factor (SF) in calculating the ADI?
How is the NOAEL typically determined?
How is the NOAEL typically determined?
Signup and view all the answers
Which of the following is a key distinction between ADI and TDI/TWI?
Which of the following is a key distinction between ADI and TDI/TWI?
Signup and view all the answers
Why is there significant debate about extrapolating the results of animal studies to humans when determining ADI?
Why is there significant debate about extrapolating the results of animal studies to humans when determining ADI?
Signup and view all the answers
Which of the following is a major concern when considering the safety of a substance?
Which of the following is a major concern when considering the safety of a substance?
Signup and view all the answers
What is a potential challenge in setting a TDI for a specific contaminant in food?
What is a potential challenge in setting a TDI for a specific contaminant in food?
Signup and view all the answers
What does risk refer to in the context of adverse effects on human health or the environment?
What does risk refer to in the context of adverse effects on human health or the environment?
Signup and view all the answers
What is a hazard?
What is a hazard?
Signup and view all the answers
Which factors contribute to environmental risk assessment?
Which factors contribute to environmental risk assessment?
Signup and view all the answers
What are the components of the risk equation?
What are the components of the risk equation?
Signup and view all the answers
Which of the following is NOT considered a form of toxicant?
Which of the following is NOT considered a form of toxicant?
Signup and view all the answers
What does the process of hazard identification aim to achieve?
What does the process of hazard identification aim to achieve?
Signup and view all the answers
Which of the following is an example of a lifestyle hazard?
Which of the following is an example of a lifestyle hazard?
Signup and view all the answers
Which term describes a combination of factors leading to potential harm in risk assessment?
Which term describes a combination of factors leading to potential harm in risk assessment?
Signup and view all the answers
What is the primary focus of nutritional toxicology?
What is the primary focus of nutritional toxicology?
Signup and view all the answers
Who is known as the 'Father of Toxicology'?
Who is known as the 'Father of Toxicology'?
Signup and view all the answers
What key principle does Paracelsus emphasize about poisons?
What key principle does Paracelsus emphasize about poisons?
Signup and view all the answers
What major topic does food toxicology focus on?
What major topic does food toxicology focus on?
Signup and view all the answers
Which of the following best describes toxicology?
Which of the following best describes toxicology?
Signup and view all the answers
Which term refers to harmful substances that may be present in food?
Which term refers to harmful substances that may be present in food?
Signup and view all the answers
What aspect does nutritional toxicology encompass?
What aspect does nutritional toxicology encompass?
Signup and view all the answers
What does the term xenobiotics refer to in toxicology?
What does the term xenobiotics refer to in toxicology?
Signup and view all the answers
What is the primary purpose of dose-response assessment?
What is the primary purpose of dose-response assessment?
Signup and view all the answers
What does LD50 represent in toxicity studies?
What does LD50 represent in toxicity studies?
Signup and view all the answers
What distinguishes dose from exposure?
What distinguishes dose from exposure?
Signup and view all the answers
Which method is NOT considered a comparative method in risk assessment?
Which method is NOT considered a comparative method in risk assessment?
Signup and view all the answers
What is the fundamental distinction between exposure and dose in toxicology?
What is the fundamental distinction between exposure and dose in toxicology?
Signup and view all the answers
Which of the following assesses the probability of hazardous events occurring?
Which of the following assesses the probability of hazardous events occurring?
Signup and view all the answers
In toxicity studies, what distinguishes hazardous agents?
In toxicity studies, what distinguishes hazardous agents?
Signup and view all the answers
Which of the following is a component of fundamental methods in risk assessment?
Which of the following is a component of fundamental methods in risk assessment?
Signup and view all the answers
What characterizes the U-shaped dose-response curve for carbohydrate energy intake?
What characterizes the U-shaped dose-response curve for carbohydrate energy intake?
Signup and view all the answers
At what vitamin D level is the lowest risk of mortality observed in the J-shaped curve?
At what vitamin D level is the lowest risk of mortality observed in the J-shaped curve?
Signup and view all the answers
What does the threshold dose indicate in relation to toxic effects?
What does the threshold dose indicate in relation to toxic effects?
Signup and view all the answers
Which of the following statements about lethal dose 50% (LD50) is correct?
Which of the following statements about lethal dose 50% (LD50) is correct?
Signup and view all the answers
What shape does the dose-response curve typically take for most health effects expressed in terms of body weight?
What shape does the dose-response curve typically take for most health effects expressed in terms of body weight?
Signup and view all the answers
What is a major limitation of LD50 tests?
What is a major limitation of LD50 tests?
Signup and view all the answers
What happens at low levels of vitamin D in the J-shaped dose-response curve?
What happens at low levels of vitamin D in the J-shaped dose-response curve?
Signup and view all the answers
What is indicated by a slight increase in risk at high levels of vitamin D?
What is indicated by a slight increase in risk at high levels of vitamin D?
Signup and view all the answers
What is the main function of albumin in the context of xenobiotics?
What is the main function of albumin in the context of xenobiotics?
Signup and view all the answers
Which phase of metabolism primarily involves cytochrome P450 enzymes?
Which phase of metabolism primarily involves cytochrome P450 enzymes?
Signup and view all the answers
What occurs during the Phase II reactions of biotransformation?
What occurs during the Phase II reactions of biotransformation?
Signup and view all the answers
Which of the following is NOT a Phase I reaction?
Which of the following is NOT a Phase I reaction?
Signup and view all the answers
What is one effect of the 'first pass' metabolism by the liver?
What is one effect of the 'first pass' metabolism by the liver?
Signup and view all the answers
Which of the following enzymes are classified as mixed function oxidases?
Which of the following enzymes are classified as mixed function oxidases?
Signup and view all the answers
How does the metabolism of benzene mainly affect human health?
How does the metabolism of benzene mainly affect human health?
Signup and view all the answers
What is a consequence of Phase I biotransformation?
What is a consequence of Phase I biotransformation?
Signup and view all the answers
Which of the following is NOT a site of biotransformation?
Which of the following is NOT a site of biotransformation?
Signup and view all the answers
Which group of dietary components can induce enzyme activity related to metabolism?
Which group of dietary components can induce enzyme activity related to metabolism?
Signup and view all the answers
What characterizes the biotransformation of a toxic substance during Phase II?
What characterizes the biotransformation of a toxic substance during Phase II?
Signup and view all the answers
Which of the following is a common mechanism in Phase I reactions?
Which of the following is a common mechanism in Phase I reactions?
Signup and view all the answers
What role do transferases play in Phase II metabolism?
What role do transferases play in Phase II metabolism?
Signup and view all the answers
Study Notes
Course Information
- Course Title: Nutritional Toxicology
- Course Code: NFS488H1-W2025
- Instructor: Dr Joan Jory RD PhD (Dr J.)
- Course site (platform): Quercus
- Announcements are posted on Quercus regularly for updates, clarifications, significant course-related reminders. Students should check daily and turn on the notifications.
- Online Discussion Boards are for questions relating to course content, materials, tests, and assignments.
- Course materials are organized into weekly modules and lecture slides, along with readings, are posted under the Modules tab.
- Assignments and test information are placed under the Assignment tab for clarity containing descriptions, deadlines, instructions, and rubrics.
- Questions about personal matters should be emailed to Dr. J.
Course Topics
- Applications of toxicology in the context of food science and nutrition
- Food and nutrient safety & regulation
- Fundamentals of toxicogenomics
- Fundamental and applied research
- Food industry
- Emerging topics: application of the omics in toxicology, mercury and toxins in First Nations food and artificial sweeteners and toxicity
- Basics concepts
- Toxins and toxicants
- Toxicology tests
- Nutrient DRIs/ Regulation
- Artificial Sweeteners/Toxicity
- Gene-food toxicant interactions
- Applied Toxicology
- Mercury, POPs and First Nations peoples
- Toxicomicrobiomics
- Drug-nutrient interactions and genetic susceptibility
Course Assessment
- Research question (2%): January 29
- Term Test 1 (Open Book) (26%): February 5
- Project Outline (3%): February 12
- Group Research Paper (20%): March 12
- Term Test 2 (Open Book) (26%): March 19
- Group Oral Presentation (15%): March 26 - April 2
- Participation (6%): March 26 - April 2
- Course engagement (2%): January 8 - April 2
- Total (100%):
Term Tests
- 1.5 hours, open book
- In-person
- No make-up tests (see syllabus for course policies)
Group Project
- Written Report (Comparison of Studies and Scientific Evaluation Proposal, Critical evaluation of a toxic substance in the food/beverage supply, Developing writing skills)
- Oral Presentation (12-minute Group Presentation, 12 minutes oral presentation + 3-5 minute question period, Developing effective oral presentation skills)
Group Assignment Topics
- Choose ONE topic related to a food or beverage toxic substance and its health outcome implications.
- A tutorial will be presented by TA Sabrina on Wednesday, January 15 at 3pm on how to be successful with the group assignment
- Groups will consist of 2-4 students.
- Create groups on Quercus.
Syllabus Reconnaissance
- Students are to individually identify TWO important details from the syllabus.
- Identify ONE item that they are excited about.
- Identify ONE question/concern from the syllabus.
Lecture 1 (January 8, 2025)
- Objectives: Understand the basic principles of toxicology, Identify toxicology phases, Understand the dose-response curves.
Definitions
- Toxicology: Study of the adverse effects of chemicals or physical agents on living organisms (poisons, toxicants, or toxins, often xenobiotics).
- Food toxicology: Studies the toxins or toxicants in food.
- Nutritional toxicology: Inter-relationships of toxins/toxicants and nutrients on diet/nutritional status and food safety - toxicity connected to the food supply.
History of Toxicology
- Paracelsus (1493-1541): Father of toxicology. Recognised that dose is an important determinant in whether a substance is a poison or a remedy.
- Orfila (1787-1853): Established relationships between chemical properties and toxic effects.
Dose-Response
- The measure describing the relationship between the exposure dose of a substance and the response to the substance.
- Determined by experiments in animals (dose in concentrations, observing animals for specific symptoms/endpoints).
Classification of Toxins/Toxicants
- Physical state: Gas, liquid, solid.
- Toxicity: Extremely, slightly.
- Chemical composition: Heavy metal, organophosphate.
- Mechanism of action: Anticholinergic*, Enzyme inhibitor, Hepatotoxin, Carcinogen. (*Anticholinergic: Blocks the neurotransmitter Acetylcholine in the brain).
Toxic Responses
- Immediate vs. delayed responses (minutes to years): Acute (single exposure, short-term), Subchronic (repeated exposure, <1.5 life exp), Chronic (>1.5 life expectancy).
- Reversible (rapidly regenerating tissues) vs irreversible (CNS damage, carcinogenesis, teratogenesis).
Local vs. Systemic
- Local: First contact target area, e.g., inhalation of irritants.
- Systemic: Absorption and distribution to a distant site, e.g., most toxicants.
Phases of Toxicological Effects
- Exposure: dissipation of toxins or formation of active toxic substance.
- Toxicokinetics: absorption, distribution, biotransformation (metabolism), excretion.
- Toxicodynamics: toxicant-receptor interaction in target tissues.
Exposure Phase
- The substance must be present in a molecular form relatively lipophilic to penetrate biological membranes.
- Bioavailability and absorption depend on the degree of ionization from the pH of the absorption site.
Duration of Exposure
- Acute (1 day)
- Sub-acute (10 days)
- Subchronic (2 weeks to 7 years)
- Chronic (7 years to lifetime).
Route of Exposure
- Ingestion, inhalation, or absorption through the skin.
- Depending on insolubility or solubility in gastrointestinal juices and fluids affect excretion.
Toxicokinetics Phase
- Absorption: entrance into the body
- Distribution: movement to locations in the body
- Metabolism/Biotransformation: chemical reaction changes.
- Excretion: Elimination from the body.
Absorption of Substances
- Factors affect absorption: dose, type, dissolution of particles and physical/chemical properties of the substance, stability of substances in the gastric/intestinal juices.
- Methods to get substance absorbed: simple/facilitated diffusion, or active transport and endocytosis.
Extent of Absorption = Bioavailability
- Portion of the dose that is destroyed by the gut wall, liver, etc., and not absorbed.
Via the blood and Lymphatic systems
- The blood and lymphatic systems transport toxic agents/substances.
- Depends on the properties - water solubility, lipid solubility, molecular weight (MW) and polarity affect distribution
- Fat-soluble substances tend to remain in body fat stores.
Distribution
- Location of toxins in the body.
- Excreted, stored, or metabolised.
- Metabolites can interact with cellular components.
Volume of Distribution (Vd)
- Represents the apparent volume that is a distributed substance in plasma and the rest of the body.
- Quantifies how evenly a compound is distributed through the body.
Take-home test
- Determining which factors influence the volume of distribution (Vd) of a substance.
Distribution: Plasma Protein Binding
- Some xenobiotics bind to plasma proteins (especially albumin), making them inaccessible to tissues.
- Only the unbound substance can leave the blood and reach a target.
Metabolism (Biotransformation): Phase I & II Reactions
- Phase I: Oxidation of, reduction, hydrolysis of substances producing more water-soluble and reactive products (using enzymes).
- Phase II: Conjugation with another substance to make it more water-soluble for excretion (using transferases).
- CYP450 enzymes most important in Phase I
Biotransformation Sites
- Liver (high concentration of bio-transforming enzymes and first-pass effect)
- Kidneys and lungs (10-30% of the liver)
- Skin, intestines, and placenta (lower capacity)
Biotransformation Phases.
- Phase 1: oxidation, reduction, hydrolysis.
- Phase 2: conjugation (using enzymes like CYP450s).
- Example: benzene's biotransformation (Phase 1 and 2 intermediates)
Excretion
- Elimination of xenobiotics and metabolites by specific excretory organs.
- Routes: urine, feces, breast milk, sweat, saliva
Rate of Excretion
- Half-life determines how much time is needed to reduce concentration in the body by half.
- Substances that remain longer in the body have a more substantial potential for adverse effects.
Toxicodynamics Phase
- Toxicants reach specific site of action (the receptor/enzyme active sites) with specific interactions.
- Mechanisms/methods of action to the body are diverse.
Mechanisms of Action of Toxic Substances
- Specific mechanisms include receptor-mediated events (e.g. receptor activation/inhibition and activation of enzymes)
- Non-specific mechanisms, include necrosis and interference with metabolism and synthesis.
Factors that Modify Toxicity
- Dose/concentration
- Age
- Gender
- Genetics
- Diet
- Health status
- Frequency/duration of exposure
- Route of administration
- Form of toxicant
- Metabolism/biotransformation
Nutritional Toxicology & Risk Assessment
- Risk evaluation to consider the social acceptability of risks, evaluating potential risks, and weighing factors like compensation, if applicable.
- Risk estimation which determine magnitude of risks, spatial scale, duration, intensity and cause-effect links.
- Risk characterization is the combination of risk estimation and exposure assessment.
Hazard Identification & Analysis
- Possible harms
- Routes of hazardous exposure
- Probability or chance of the incident occurring
- Data collection and analysis.
Dose-Response Assessment
- Understand the relationship between the dose of an agent and its effects.
- Differences in toxicity of contaminants as the dose changes.
- How dose response assessment is critical in addressing the question, “What are the health problems at different doses?”
Dose
- Measured amount of an agent per unit body weight per day. (Units: mg/kg/day).
LD50
- Lethal dose (50%) - The dose that causes death in 50% of test animals
- Useful in determining acute toxicity only (short term)
NOAEL
- No Observable Adverse Effect Level - Highest dose without observed adverse effects.
LOAEL
- Lowest Observable Adverse Effect Level- Lowest dose where there are observed adverse effects.
Acceptable Daily Intake (ADI)
- Amount of a substance humans consume daily over a lifetime without adverse health problems.
- Based on NOAELs in animals and uncertainty factors to account for differences.
Tolerable Daily Intake (TDI)
- Amount of a substance, either in daily intake (TDI) or weekly intake (TWI). The goal is to determine for chemical contaminants if the intake does NOT cause harm to humans
Maximum Residue Level (MRL)
- Maximum permissible amount of a chemical found in a crop when it is sprayed with an agrochemical (e.g., pesticides).
- MRLs are determined by organizations like Codex Alimentarius (FAO and WHO).
Take-home test
- Students to interpret and analyze dose-response plots.
Exposure Assessment
- Understanding the extent to which environmental compartments are exposed to a hazard.
- Establishing the link between exposure and the risk.
Magnitude, Frequency and Duration
- Characteristics of the exposure to help evaluate the health of population.
Risk Characterisation
- Characterization of the incidence and severity of adverse effects.
- Quantifiable likelihood of risk occurrence.
Risk Estimation
- Assessing the magnitude of risks, spatial scale, duration and intensity of potential adverse consequences.
Risk Evaluation
- Judgment on the significance and acceptability of risk.
- Determining social acceptability; if any compensation is applicable; based on the evaluation.
Risk Management
- Use the results of risk assessment to reduce/prevent risks.
- Defining hazard, exposed populations, and adverse effects and working to improve and mitigate consequences.
Additional Considerations
- Various slides include graphs, charts, and figures that illustrate and clarify the concepts.
- Multiple examples of substances, including benzene and aspirin, are used to illustrate the principles and methodology of toxicity studies.
- The course emphasizes the importance of assessing health concerns from a variety of perspectives.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
Test your knowledge on key concepts in toxicology, including the definitions and applications of LOAEL, ADI, NOAEL, and TDI. This quiz will challenge your understanding of risk assessment, hazard identification, and environmental considerations in human health. Explore the distinctions between various toxicological terms and their significance in health safety.
