PUBH 6011 FINAL EXAM

PUBH 6011 FINAL EXAM "The dose makes the poison" - ANSWER- - A substance's toxicity depends on not only its chemical identity, but also on its quantity - "All substances are poison and nothing is without poison, only the dose permits something to not be poisonous"" How do we learn about toxicity? - ANSWER- - animal studies - epidemiology Epidemiology - ANSWER- - study of disease rates in human populations with and without exposure to chemical under study - can discover statistical association between exposure and disease - rarely can establish a causal relationship or mechanism of disease causation Epidemiology: Strengths and limitations - ANSWER- Strengths: - study species of interest - free ranging subjects in their natural environment Limitations: - non-experimental - often qualitative - usually retrospective - often high-dose occupational studies (environmental exposures often much lower; may miss diseases of women/young/elderly) - subject to confounding and bias What is toxicology? - ANSWER- - study of adverse effects in biological systems caused by chemical or physical agents - assess the likelihood of the occurrence of adverse effects - study the nature and mechanisms of adverse effects - uses model to stand in for people Animal testing - ANSWER- - tests on rodents to assess adverse effects - rodents chosen for short life, small size and easy care - tests can address acute, subchronic or chronic toxicity Toxicology animal testing - ANSWER- Strengths: - well controlled (doses, no confounding exposure) - prospective Questions: - generalized across species -high dose to low dose extrapolation - definition of response Dose-response relationship - ANSWER- - toxicity quantified through the dose-response relationship - individual: change in severity of effect with dose - population: change in prop. of population responding with dose --- different for different effects --- shape of curve gives information about pop. variability and tox of the compound Population dose-response function - ANSWER- - focus on a specific endpoint - test multiple individuals (mice or rats usually) at specific doses - at each dose level, individuals either do or don't respond (variation across individuals) - measure proportion of population responding at each dose level or level of response at each dose level - as dose goes up, severity goes up Variation in response to dose - ANSWER- - differences in response due to genes, nutrition, health status, etc. Tolerance distribution - ANSWER- more of the population will respond at higher doses, more of the population has tolerance to low doses How does an agent get into the body - ANSWER- route: - oral - dermal - inhalation timing: - acute (days) - sub-chronic (weeks to months) - chronic (months to years) Equivalent doses - ANSWER- - use mg/kg to make equivalent doses across species Acute toxicity - ANSWER- adverse effects that occur within a short period after exposure to a toxicant; often reversible, usually from a single dose Chronic toxicity - ANSWER- adverse effects that occur some time after exposure to a toxicant or after extended exposure to the toxicant; ex cancer, liver damage, lung fibrosis Local toxicity - ANSWER- toxic effect occurs at the site of exposure (ex pulmonary edema, acid on skin) systemic toxicity - ANSWER- requires absorption and distribution of the toxicant (usually in the blood stream) to susceptible organs where the effect occurs; adverse effect is somewhere other than where the initial exposure occurred Exposure pattern influencing dose response - ANSWER- acute toxicity: happens quickly - usually after 1 dose - include death, CNS effects, irritation, etc. Chronic: - result of prolonged exposure, usually lower doses than acute - organ damage, cancer - eventually it will build up to a point where the adverse effect occurs frequently little relationship between the two Pharmacokinetics influencing dose response - ANSWER- can differ by species, sex, age, nutrition, disease, enzyme induction (prior exposure) - how the body responds to a specific dose/exposure DDT LD50 in rats - ANSWER- - newborn rats have a higher tolerance for DDT - the lower the LD50, the more toxic the chemical is (bc it takes less of it to have effects) - age influences toxicity/response in either direction Species and strain in dose response - ANSWER- - can differ between strains due to different mechanisms of action/different receptors between species - common to assume that humans are the most sensitive when studying and use the most sensitive species to begin studying the chemical LD50 - ANSWER- - dose (mg/kg) lethal to 50% of test animals - determined orally, through inhalation or by dermal exposure LC50 - ANSWER- - concentration (in ppm or mass/volume) lethal to 50% of test animals - something in the water, air, etc. where you can measure the concentration in the environment Subchronic/chronic tox testing - ANSWER- - concerned with long term exposure to lower doses - test for damage to certain organs - damage to functional systems (neuro, immuno, etc.) - test for carcinogenicity Mechanic studies - ANSWER- - study of potential models of action in lab animals (in vivo) or with isolated tissues, cells or components (in vitro) strengths: - compound specific info - understanding biology should improve problems: - difficult to rule out alternative theories - lack necessary data for humans Assessing risks - ANSWER- - personal: risk of walking, driving, etc. - public health - occupational health: setting workplace standards - architects: risk of structure injuring people, earthquakes - medical: risk of side effects from new drugs - dept of transportation: traffic, hazardous material transport