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Toxicology Definitions.docx

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TOX 2000
Aaron Witham

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 K owOctanol 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 [ ] [ ] BFC= K ow x % by weight of fat in the organism Biomagnification- increasing concentration of toxicant going up the food chain ie. DDT low in H 2 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= k /1k +2 ) 3 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) LD - lethal dose for 50% of population 50 LC -50ethal concentration for 50% of the population x variable transformed into log 10ose), 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, LD 50ntilog(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 LD 50ly refers to LD do50nt reveal potencies at responses other than 50% Environmental toxicology- protect the population ie LC 5 Human toxicology- protecting individuals ie benchmark dose Benchmark dose- corresponds to defined benchmark response 10 -6 Limitations with LD 50 Values obtained in one species cannot be directly translated into other species Lethality rarely appropriate toxic endpoint but measures such as LD 5n 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 Habers 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 complexnsituations: o c x t = 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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