Published on 18 Jul 2011
Department
Environmental Science
Course
EESA10H3
Professor
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
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
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????
www.notesolution.com
•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
www.notesolution.com
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.