Lower doses might include \u00bd or \u00bc of the MTD Extensive histopathology

Lower doses might include ½ or ¼ of the mtd

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Lower doses might include ½ or ¼ of the MTD-Extensive histopathologyExposure/Dose-Response Relationship-Dose response curve for carcinogen must go thru zero, but rarely does because we have background risk to increase base risk-Virtually safe dose: level of exposure for carcinogen not associated with increased risko1 in a million or between 1 in 100,000 or 1 in a million (according to WHO)-1 cigarette once in your life won’t cause cancer, because exposure is so low1.superlinear a.more than a common increase in effect in increase in dose2.linear: 1:13.sublinear a.reduces risk, every increase in exposure, less increase4.threshold a.prescription drugsb.some level of exposure, where there is 0 effect
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Carcinogens-characterized by “no threshold” dose response relationship – some level of risk, even if itcannot be measured, at every level of exposure. (but false – very low threshold won’t cause cancer like cigarette example)Low dose extrapolation models-probit model: pretty much everything is safe-multi stage model: everything is not safe-model selection mattersAssumptions in Cancer Risk Assessment-dose response from limited size groups of experimental animals (homogeneous identicallab animals), can predict dose response relationship for heterogeneous human population – not reasonable because we are all different, not like homogenous lab animals-dose-response data obtained at high levels of exposure relative to expected environmental exposures can predict dose-response relationship at lower doses-dose-response data obtained from consistent experimental dosing (same amount of dosage every day for however long) can predict dose-response relationships for much more variable human exposures – not true because we don’t take an exact consistent amount of dosage every day for yearsExperimental carcinogenicity data sufficient evidence of carcinogenicity:-casual relationship has been established between the agent and an increased incidence of malignant neoplasms in:oa) two or more animal species or ob) in two or more independent studies in one species carried out under different circumstancesLimited evidence of carcinogenicity-not as strong as sufficient-data suggests a carcinogenic effect but not limited for making a definitive evaluation because othe evidence of carcinogenicity is restricted to a single experimentothere are unresolved questions regarding the experimentothe agent increases the incidence of only benign neoplasms or lesionsGroup 2-this category includes agents for which, at one extreme, the degree of evidence of carcinogenicity in humans is almost sufficient as well as agents for which, at the other extreme, there is no human data but for which there is experimental evidence of carcinogenicity
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-agents are assigned to either 2A (probably carcinogenic)-or 2B (possibly carcinogenic) on the basis of epidemiological, experimental, and other relevant dataGroup 2A-the agent is probably carcinogenic to humans. This category is used when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals-
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