EESA10H3 Lecture Notes - Risk Assessment, Median Lethal Dose, Chronic Toxicity

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18 Apr 2012
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HUMAN HEALTH AND ENVIRONMENT Lecture 9: Toxicology and Risk Assessment
***majority of questions on final exam and hardest questions on final exam will come from this lecture
Toxicology
-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)
Assessing chemical hazards
-how harmful a substance depends on:
-checmical properties of the substance
-electronegativity
-polarity
-oxidation state
-molecular weight
-dissociation
-solubility
-water soluble toxins (mostly inorganic) unable to penetrate cell wall stay
between cells and this what they effect
-fat soluble toxins (mostly organic toxins) able to penetrate cell wall and
enter the cell and harms within the cells
-persistence of a chemical easy/slow breakdown of chemicals in body/environment
-i.e. DDT desirable to be persistent to kill insects but not desirable to be persistent in
the environment and human body
-bioaccumulation build up of the chemical over time in tissues and organs
-biomagnification build up of chemicals in the food chain over time (animals at the bottom of
the food chain have lower amounts of chemicals and animals higher in the food chain have
higher amounts of chemicals
-chemical interaction interaction between chemicals can reduce or increase toxicity
-antagonisticpresence of one chemical reduces the toxicity of another i.e. vitamins E
and A can slightly reduce carcinogenic effects of some chemicals
-synergistic presence of one chemical increases the toxicity of another i.e. if an
individuals who is exposed to asbestos and is a smoker increases their risk of cancer 400
folds
-receptor
-dose
-response
Receptor
-who’s receiving exposure or dose humans, animals plants
-frequency of exposure how often
-age age is also directly related to general health
-general health
-genetic makeup consequences to exposure will differ among indivudals
Dose
-the amount of substance a person has:
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-ingested (often the greatest source of chemical exposure 85%0)
-inhaled (air pollution, particles and volatiles, 10%)
-absorbed through the skin (industrial 5%)
-debate about actual amount that receptor sites “sees” vs. amount take in we excrete and
breakdown the chemicals
-acute dose refers to single dose, usually high
-chronic dose repeated or continuous low dose over time i.e. radiation
-long term low dose over a life time
Response
-symptoms and illness that someone can observe and record as a result of exposure two groups:
specific and nonspecific
-nonspecific whole body/system has been affected no particular organ is affected, whole
system is
-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 expressed in percent mortality
-chronic toxicity
-Paracelsus’ principle “the dose makes the poison.”
-every chemical can be toxic, it’s just the question of what amount
-i.e. water about 3 L of water can have very serious health consequences
-how much exposure causes a harmful response?
-affects differently for different individuals
Measuring manifestations
-endpoint physiological manifestation first one that can be readily measured
-use of “biomarkers” i.e. changes in hormone level, protein markers, enzyme induction
Methods for determining toxicity
-laboratory experiments on animals (mice and rates)
-it is important to calculate the lethal dose (LD50) of a chemical and the dose response curve
-dose response is the graded response as a function of dose how does response change in dose
increases/decreases
-the lethal dose can be determined from the dose response
-you can find out the lethal dose of a chemical rom case reports (accidental poisoning, attempted
suicide), epidemiological studies, computer simulations, tissue cultures of cells and bacteria (testing on
animals)
-dose response uses acute toxicity tests (on animals) high dose over a short period of time)
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Dose Response Curve
-green is non-threshold chemicals does not have a threshold mortality happens immediately with
application of first dose
-no safe dose
-red is threshold chemicals increasing the dose does not result in death (UP TO SOME POINT) after
which, there will be deaths of the animals which will increase significantly until all the animals are dead
(100% mortality)
-there can be a safe dose amount
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