3 risk assessment Flashcards
what did paracelsus say?
the dose defines the poison
-“ the universities do not teach all things, so a doctor must seek out old wives, gypsies, sorcerers, wandering tribes, and such outlaws and take lessons from them”
what is the terminology of risk assessment and risk?
-risk assessment: the systematic scientific characterization of potential adverse health effects resulting from human (or non-human biota) exposure to hazardous agents or situations
-risk: the probability of an adverse outcome
what is the terminology of risk management and risk communication?
-risk management: the process by which policy actions (regulations) to deal with the hazards identified in risk assessment are chosen
-risk communication: the process of making risk assessment and risk management information comprehensible to “nonscientific people” (e.g. lawyers, lay public, stakeholders)
what are the objectives of risk assessment?
what are the four steps in risk assessment?
- hazard identification: is there a potential risk?
- dose-response assessment: determine toxicity thresholds
- exposure assessment: routes of exposure, level of exposure
- risk characterization: combines dose-response assessment and exposure assessment to characterize xenobiotic risks
what is the framework of risk assessment vs. risk management?
________________________ are continually evolving
risk assessment and risk management
what is dose-response assessment?
-“quantitative risk assessment”: characterization of dose-response curves to determine toxicity thresholds (e.g. NOAEL, ED20, etc)
-problem: need to extrapolate high doses animal bioassay data to low dose human exposures
-solution: use low dose extrapolation methods and safety factors
what are some dose-response assessment terminology (NOAEL, LOAEL)?
-no observed adverse effect level (NOAEL): in a dose-response curve, the highest dose that does not produce a significantly elevated incidence of adverse response compared to control
-lowest observed adverse effect level (LOAEL): the lowest dose that produces a significantly elevated incidence of adverse response compared to control
what does ADI and TDI mean (dose-response assessment terminology)?
acceptable daily intake (ADI) and tolerable daily intake (TDI): the daily intake of a chemical, which during an entire lifetime, appears to be without appreciable risk, based on currently available scientific information
-ADI is for food additives, pesticides and drugs
-TDI is for xenobiotics with no reason to be in food (e.g. industrial contaminants)
-USEPA uses reference dose (RfD), which is the same as ADI/TDI
a safety factor of _______________ is most commonly used in huma health risk assessment
100 (10 x 10)
what is the graph of exposure assessment?
what is exposure assessment terminology?
-lifetime average daily dose (LADD)
-high-end exposure estimate (HEEE)
-short term exposure limits (STEL)
what is LADD?
the average dose that humans are exposed to on a daily basis for their entire life
-LADD is compared to the ADI or TDI in order to determine if there is a toxicological risk to humans; if LADD > ADI/TDI then risk managers must make policy decisions to reduce human risk
what is HEEE and STEL?
-high-end exposure estimate (HEEE): the upper 90th percentile of exposures in the human population
-short term exposure limits (STEL): used in occupational settings for acute exposure to chemicals, mainly industrial solvents
what is a risk assessment example? (not all on exam)
-halogenated aromatic hydrocarbons (HAHs) are highly lipophilic, resistant to biotransformation and environmental degradation, and extremely toxic (carcinogenic and teratogenic)
-HAHs include dioxins, furans and polychlorinated biphenyls (PCBs)
-due to common mechanism of action (binding to aryl hydrocarbon receptor; AhR), the concentrations of individual dioxin-like chemicals in food (>100 chemicals) can be simply added together
what is the equation for LADD?
LADD is used for exposure assessment
what is the example of calculating LADD?
what is the TDI for dioxin-like chemicals?
did not want dioxin-like chemicals to show up in food
-TDI for dioxin-like chemicals varies greatly among jurisdictions (due to differences in low dose extrapolation methods)
what about ecological risk assessment?
-same principles as human health risk assessment, but modified to include more detailed science on environmental fate, interactive effects of toxicants and other stressors, predator-prey relationships, food web dynamics, etc
-different levels of complexity involved
-different acceptable risks involved: in ecorisk assessment we are focused on protecting populations and communities of non-human species, whereas in human health risk assessment we are focused on protecting individual humans
-societal and political questions involved: what level of ecosystem impairment are we willing to accept?
why is acrylamide of concern? should we be worried?
-produced when heating up organic material
-CYP2E1 gets induced by ethanol
-well paracelsus told us dose defines the poison
what is risk perception?
how humans perceive risk
what is the graph of risk space?
includes things that are you cannot observe
final
-twice as long as midterm
-out of 200 marks
-first 100 is like midterm of third topic (teratogenicity, carcinogenesis, target organs, dose-response, etc): pretty evenly distributed
(25 on tera, 25 carco, 25 on risk asses, 25 on target)
-other 100 is based on the entire course (100 marks):
-why is the liver a target organ? (six reasons) (or lung, kidney)
-rat vs mice question (asks for 6): can be environment, genetic factors (ADME differences, toxicodynamics (response: expression of repair mechanisms, enzymes, etc))
-most of questions besides long answer will be short answer, fill in blank, multiple choice, matching
-might be a question on drawing the biotransformation of an enzyme
