EESA10H3 Lecture Notes - Lethal Dose, Chronic Toxicity, Risk Assessment
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Lecture 9: Toxicology
– Study/Science of poisons
– “the science which studies toxic substances or poisons, that are substances which cause
alteration or perturbation in the function of an organisms leading to harmful effects
-Some times people are working with toxic substances without being aware of it.
Toxicology: assessing chemical hazards (1)
• How harmful a substance is (toxicity) depends on:
– Chemical properties of the substance, how much of the substance would be found in the water,
soil, air. Volatile substances are found in air.
Chemical partition in the environment depends on:
• Electro negativity
• Oxidation state
• Molecular weight
• Dissociation: cations and anions (distribution is different)
– Water soluble toxins: inorganic substances like heavy metals are water soluble
– Fat soluble toxins (like organic toxicants like DDT)
Toxicology: assessing chemical hazards (2)
• Persistence of chemical – break down environment
• Bioaccumulation: accumulation in some organ. Nothing to do with food chain.
• Biomagnification: increased concentration of chemical in organism food chain.
• Chemical interaction between 2 chemicals. How much they can be toxic
– Antagonistic: In presence of carcinogen with Vitamin A/E, that can significantly reduce their
– Synergistic: If 2 chemicals are found together, it can cause even more harm. Eg. Asbestos +
smoking for lung cancer
• Multiple chemicals – food additives, pesticides, air pollution
1. Receptor – organism receiving exposure or dose
• Frequency of exposure
• General health
• Genetic makeup: transferred genes from the parents and ancestors
2. Dose – the amount of substance a person has
Every chemical is poison if exposed to a certain level.
• Ingestion (often greatest source of chemical exposure, 85%)
• Inhalation (air pollution, particles and volatiles, 10%)
• Absorbed through the skin (industrial, 5%)
• Debate about actual amount that receptor site (enzymes, proteins, hormones, lipids etc) “sees”
vs. amount taken in
– Acute dose – refers to single dose, usually high
– Chronic dose – repeated or continuous low dose over time
– Long term – low dose over a life time
3. Response: what we see, what symptoms are shown
– Burning – destruction of cells caused by exposure to high concentration of strong acids
– Narcosis – depression in sensory activity, reversible, caused by alcohols, ethers,
• Specific: certain tissue that experiences harm
– Damage to excretory organs
– Damage to respiratory organs
– Damage to reproductive function
• Acute toxicity– rapid death or dramatic response
• Chronic toxicity: long time but mild symptoms
• Every chemical is harmful at some level of exposure: usually Ca 2+ not considered harmful. 3L
of H2O at once can cause death and about
• How much exposure causes a harmful response??
• Endpoint – when someone uptakes the chemical in the body - toxicological manifestation.
Very hard to measure as we don’t know what to measure. Some symptoms we can usually see is
needed. In toxicology, a quantifiable biological change or effect caused by a toxic process.
• Measurement Endpoint – physiological manifestation
– Can be readily measured
– More easily measured than endpoint
– Use of “biomarkers” e.g. changes in hormone levels, protein markers, enzyme induction i.e.
something that makes it easy to detect.
Methods for determining toxicity
– Laboratory experiments on animals (mice and rats)
Lethal dose (LD50): Dose that group of animals receives as a single dose that will cause
mortality of 50% of examined individuals in period of 14 days
– Case reports from doctors, physicians
– Epidemiological studies: Study of epidemic control group and other group which we are
testing (somehow exposed to the chemical)
– Computer simulations: grey pics and crap. Many stuff see from them to define important
– Tissue cultures of cells and bacteria
– Acute toxicity tests are used
– Graded response as a function of dose
– In population – significant number of people.
Dose-Response curves: have to be designed for each chemical. For most chemicals we already
Graph description: When dose increases (in ppm or ppb) on the x-axis and the % response on the
y-axis. 2 types of chemicals: non-threshold and threshold.
The science which studies toxic substances or poisons, that are substances which cause alteration or perturbation in the function of an organisms leading to harmful effects (truhaut,1974) Some times people are working with toxic substances without being aware of it. (1) Toxicology: assessing chemical hazards: how harmful a substance is (toxicity) depends on: Chemical properties of the substance, how much of the substance would be found in the water, soil, air. Chemical partition in the environment depends on: electro negativity, polarity, oxidation state, molecular weight, dissociation: cations and anions (distribution is different, solubility. Water soluble toxins: inorganic substances like heavy metals are water soluble. Fat soluble toxins (like organic toxicants like ddt) Toxicology: assessing chemical hazards (2: persistence of chemical break down environment, bioaccumulation: accumulation in some organ. Nothing to do with food chain: biomagnification: increased concentration of chemical in organism food chain, chemical interaction between 2 chemicals.