Week 10 Lecture

17 views8 pages
Published on 18 Jul 2011
School
UTSC
Department
Environmental Science
Course
EESA10H3
Toxicology
Toxicology
Definition:
Study 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
(Truhaut, 1974)
Poisons are compounds and cause negative impacts on human health
Subject of research in toxicology: from the sources of these poisons, the
composition, the partition in the environment, exposure (how someone gets
exposed to this), from which source, how much (dose), what kind of response
human body can have, chemistry of the poison
Toxicology: assessing chemical hazards (1)
How harmful a substance is depends on:
Chemical properties of the substance
Electronegativity
Polarity water is polar (has negative and positive side), all chemicals that
are polar dissolve well in water
While non-chemicals are not dissolvable in water
Relates polarity to solubility
Polar chemicals mostly stay between the cells in human tissues,
they are not able to penetrate through the cell walls because they
have fats (non-polar)
While the non-polar chemicals are soluble in fats, they are able to
go through the cell wall and enter the cell
Oxidation state
Molecular weight
Dissociation
Solubility
Water soluble toxins
Fat soluble toxins
Toxicology: assessing chemical hazards (2)
Persistence of chemical (i.e. DDT we want to have a prolong effect of DDT to protect the
crops, but from an environmental perspective, persistence is not something we prefer/like)
Bioaccumulation = chemicals accumulate in particular tissues in the human body
(muscles, brain, hair)
Biomagnification = building up the level of the chemical in the food chain (i.e. animals at
the top of the food chain are the highest to have the highest level of chemicals in their
bodies)
Chemical interaction (chemicals are always exposed to more than one chemical at the
same time, interaction can reduce or increase toxicity)
Antagonistic = when one chemical reduces the toxicity of another one
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Some vitamins (A and E) may reduce human reaction to some carcinogens
Synergistic = when two chemicals are together, one of them become more toxic
E.g. smoking in the presence of asbestos
Multiple chemicals food additives, pesticides, air pollution
Receptor
Dose
Response
Toxicology: Receptor (i.e. human being or any animal or plant, anything)
1. Receptor organism receiving exposure or dose
Frequency of exposure
Age
General health chronic disease, heart disease, asthma that may increase the
vulnerability of the person
Genetic makeup maybe one person will be more susceptible while others are not
Toxicology: Dose
2. Dose the amount of substance a person has:
Ingested (often greatest source of chemical exposure, 85%)
Inhaled (air pollution, particles and volatiles, 10%)
Absorbed through the skin (industrial, 5%)
Debate about actual amount that receptor site 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
Toxicology: Response
3. Response
Nonspecific affects the whole body system
Burning destruction of cells caused by exposure to high concentration of strong
acids or bases
Narcosis depression in sensory activity, reversible, caused by alcohols, ethers,
benzene
Specific
Damage to excretory organs
Damage to respiratory organs
Damage to reproductive function
Mutagenesis
Carcinogenesis
Acute toxicity rapid death (usually acute dose causes acute toxicity)
Chronic toxicity related to chronic dose e.g. cases of cancer
Paracelsus principle: The Dose Makes the Poison
Every chemical is harmful at some level of exposure
How much exposure causes a harmful response????
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Every chemical can be toxic, but it depends on the dose
E.g. coffee hundreds of coffee contain lethal level of caffeine, they will
definitely result in death
About one hundred pills of aspirin is lethal
1 litre of ethanol is lethal too
About 3 litres of water can cause very serious effects
Differently for different individuals
The dose of a usually unknown mixture of chemicals
Measuring manifestations
Endpoint (our bodies are responding because there is something wrong) - physiological
manifestation
Can be readily measured
Use of biomarkers e.g. changes in hormone levels, protein markers, enzyme
induction
Methods for determining toxicity
Case reports from family physicians, medical doctors, real life situations, etc.
Epidemiological studies cannot be done on people
Computer simulations not excellent but still useful
Tissue cultures of cells and bacteria
Best method: Laboratory experiments on animals (mice and rates)
Lethal dose (LD50) = the dose received as the single dose that causes the mortality
of the 50% of the experimental animals within 14 days
Control group that will not be exposed to dose and other groups that will
be exposed, will be observed for 14 days
Dose-Response
Acute (one dose) toxicity tests are used
Graded response as a function of dose
Dose- Response curves (must read LD50 of the graph)
On horizontal axis = dose; vertical axis = response (e.g. mortality %)
Dose response curves should be done to every chemical, every chemical
should have their own curve
The chemical that is a lower dose but has the same LD50 is more toxic
A Non-threshold chemical
From the very beginning, with a tiny dose, there are some cases of mortality
B Threshold chemical
With increase of the dose, response stays zero but no death
Risk Assessment
What is Risk? Everything brings us some risk
Risk - possibility or probability of suffering harm from a hazard
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Document Summary

Toxicology: assessing chemical hazards (1: how harmful a substance is depends on: Antagonistic = when one chemical reduces the toxicity of another one www. notesolution. com: some vitamins (a and e) may reduce human reaction to some carcinogens. Synergistic = when two chemicals are together, one of them become more toxic: e. g. smoking in the presence of asbestos, multiple chemicals food additives, pesticides, air pollution, receptor, dose, response. 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. Toxicology: response: response, nonspecific affects the whole body system. Burning destruction of cells caused by exposure to high concentration of strong acids or bases. Narcosis depression in sensory activity, reversible, caused by alcohols, ethers, benzene: specific. Carcinogenesis: acute toxicity rapid death (usually acute dose causes acute toxicity, chronic toxicity related to chronic dose e. g. cases of cancer.

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