Toxicology Risk Assessment Quiz

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.