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TOX 2000 Study Guide - Persistent Organic Pollutant, Probit, Bioconcentration


Department
Toxicology
Course Code
TOX 2000
Professor
Aaron Witham

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Toxicology Definitions:
Toxicity- any adverse effect
Bioassay- Measurement of the potency of a substance by its effect on living cells.
Toxicant- any substance that can cause a toxic effect
Toxin- toxicant of natural origin
Xenobiotic- Relating to or denoting a substance, typically a synthetic chemical that is foreign to
the body or to an ecological system.
Target organism- the unwanted pests you intend to kill
Therapeutic Index- comparison of the amount of a therapeutic agent that causes the therapeutic
effect to the amount that causes death or toxicity
Bradford Hill:
1. Strength of association (relative risk towards exposed and unexposed populations)
2. Exposure/response (severity of response increases with increasing exposure?)
3. Temporality- (did exposure X always precede exposure Y?)
4. Consistency and specificity (does exposure to X always yield same adverse effect Y?)
5. Biological Plausibility ( reasonable mechanism by which agent X could have produced
effect Y)
6. Experimental evidence (experiments in model systems demonstrate toxic effect and
support proposed mechanism)
Fundamental laws of Toxicity:
1. No toxicity without exposure
2. Dose makes the poison non-toxic, slightly toxic, very toxic
Hormesis- opposite effect in low doses as in high doses (threshold)
Partition constant- ration of concentrations of a compound in a mixture of 2 immiscible phases
at equilibrium ie. Measure of the difference in solubility of the compound in these 2 phases
Kow- Octanol and water partition constant; octanol has same C:O as most lipids; if ≥5000 likely
to bioconcentrate
Bioconcentration factor- concentration of particular chemical in a biological tissue per
concentration of that chemical in water surrounding that tissue
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BFC= Kow x % by weight of fat in the organism
Biomagnification- increasing concentration of toxicant going up the food chain ie. DDT low in
H2O high in gulls
Persistent organic pollutants (POPs)- chemical compounds and mixtures including industrial
chemicals that persist in the environment and resist degradation through natural processes;
halogenated, distribute globally if slightly volatile, accumulate in polar regions due to
grasshopper effect
Pharmacokinetics- what the body does to the drug
Toxicokinetics- description of what rate a chemical will enter the body and what happens to it
once inside the body
Depuration- sum of the loss processes, removal of impurities, rate of depuration increases as
concentration increases
BFC= k1/(k2+k3) = c(fish) / c(aq) in accumulative poisons: Big BCF slow rate of depuration
Rate = k x concentration
k1 x c(aq) = (k2 + k3) x c(fish)
LD50- lethal dose for 50% of population
LC50- lethal concentration for 50% of the population
x variable transformed into log10 (dose), y variable transformed into probit (p)
probit- a unit of measurement of statistical probability based on deviations from the mean
of a normal distribution
50% is probit , set y=5 in least squares regression line Y=a+bX, X=(5-a)/b,
LD50=antilog(X)
Used where phenomenon is saturable
LO[A]EL- lowest observed (adverse) effect level- lowest concentration an effect is observed
NO[A]EL- no observed (adverse) effect level- highest concentration in which nothing is
observed
Depends on chosen concentration, single point data- not very reliable
LD50 only refers to LD50 doesn’t reveal potencies at responses other than 50%
Environmental toxicology- protect the population ie LC5
Human toxicology- protecting individuals ie benchmark dose
Benchmark dose- corresponds to defined benchmark response 10-6

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Limitations with LD50:
Values obtained in one species cannot be directly translated into other species
Lethality rarely appropriate toxic endpoint but measures such as LD5 in population tox to
infer concentrations that might be close to NOAEL
Requires animal testing
Probit curve for lethality cannot estimate endpoints such as carcinogenicity and
teratogenicity
Carcinogenicity- ability or tendency to produce cancer
Teratogenicity- ability to cause birth defects
Risk- likelihood bad thing will happen
Risk= hazard x exposure
Haber’s Rule-concentration x exposure = constant (percentage that were adversely affected)
Very general acute lethality
Toxicity depends on total number of molecules of toxic agent to which animals are
cumulatively exposed to
More complex situations:
o c x tn = constant where n is highly variable, time is most important
Threshold limit values (TLV) - maximum concentration of a chemical allowable for repeated
exposure without producing adverse health effects
Epidemiology- study of causes, distribution, and control of diseases in populations; comparing
exposed vs. unexposed
Relative risk- probability that a given exposure will lead to toxicity compared with probability
that toxicity will occur in the absence of exposure
RR = probability of disease in exposed / probability of disease in unexposed
ex. Smoking and thromboembolism
large RR- condition very rare without exposure ie. Mesothelioma among asbestos
workers, phocomelia among children whose mothers had taken thalidomide
Odds ratio- ratio of the odds of toxicity in the exposed group to the odds of toxicity in the
unexposed group
OR = odds of disease in exposed / odds of disease in unexposed
OR and RR are similar in magnitude when condition under study is relatively rare
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