Risk Assessment Flashcards
what is risk assessment
systematic scientific characterization of potential adverse health effects resulting from human exposure to hazardous agents or situations
what is risk
the probability of an adverse outcome under specified conditions
what is risk management
process by which policy actions are chosen to control hazards
who decides policy decisions and actions
potilics
what are the 3 main components of risk determination/ judgement
research, risk assessment, risk management
what are 4 main things that happen in risk assessment
- hazard identification
- dose response assessment
- exposure assessment
- risk characterization
what are 4 objectives for risk assessment
- protect human and ecological health
- balance risks and benefits
- set target levels of risk (food contaminants, water pollutants)
- set priorities for program activities (manufacturers, agencies)
what are the 4 four types of testing done to assess toxicity
- structure/ activity relationships
- in vitro and short term tests (cell culture, isolated tissue)
- in vivo animal bioassays
- epidemiological studies
what is a con for in vivo animal bioassays
expensive and long term
what is a pro for structure/ activity relationships
inexpensive
what is QSAR
quantitative structure activity relationships
what do QSARs do (GENERAL)
identify potential toxicities
what kind of things do they look at with QSAR
structure, solubility, stability, pH sensitivity, electrophilicity, volatility and reactivity
what is an example of a structural property that QSAR would flag
amine group on aromatic
so why would QSAR flag an amine group on aromatic
because experience shows that chemicals like this have been previously linked to cancer and DNA mutation in general
why might QSAR have mixed results
- difficult to predict activity across diff chemical classes
- difficult to predict multiple toxic outcomes based on limited testing (so many diff types of diseases)
what is a good way to increase QSAR accuracy
incorporate expert evaluation into the screening process
what is Ames test
bacterial to see ability to cause mutation
what is the best way to find evidence for toxicity in humans
epidemiological studies
what do epidemiological studies show
association between exposure and disease
what are the 3 kinds of epidemiological studies
cohort, case-control, cross-sectional
what is the initial classification in cohort studies (who is in it and how many)
exposure vs non exposure (large population)
what is the initial classification in case-control studies (who is in it and how many)
disease vs non disease (small group)
what is the initial classification in cross-sectional studies (who is in it and how many)
either exposure vs non exposure or disease vs non disease, often large populations
what is the time sequence in cohort studies
prospective (follow them for some time, check back for decades)
what is the time sequence classification in case control studies
retrospective (starting with people who already have disease, ask about the past)
what is the time sequence in cross sectional studies
present time
what is the comparison in cohort studies
exposed that develop the disease vs non exposed that develop disease
what is the comparison in case control studies
people with disease that were exposed vs. non-diseased people that were exposed
what is the comparison in cross sectional studies
people with disease that were exposed vs. non-diseased people that were exposed
OR
exposed that develop the disease vs non exposed that develop disease
what is the advantages in cohort studies
lack of bias in exposure(people choose what they do), powerful statistics that can support causation
what is the advantages in case control studies
inexpensive, small n, no attrition, good for rare diseases
which epidemiological study can support causation
cohort
what is the advantages in cross sectional studies
quick results, can determine prevalence (proportion of population with a disease/condition), can do studies with info gathered for other purposes
what is the disadvantages in cohort studies
long follow up, attrition, costly, large populations, poor for rare diseases (not big enough sizes to catch rare diseases)
what is the disadvantages in case control studies
biased recall, problems obtaining good controls, population enriched with survivors(toxin may seem better than it is, you cant interview dead people), cannot support causation
what is the disadvantages in cross sectional studies
population enriched with survivors, poor for rare diseases, hard to know if disease or exposure came first
why is it a disadvantage to have “population enriched with survivors”
it means that the toxin may seem better than it is, you cant interview dead people
why is it hard to get good controls in case control studies
cause you want people to have lived very similar lives, but some dont have the disease - hard to find
which epidemiological study can be good for rare diseases
case control
which epidemiological study can do prospective studies
cohort
which epidemiological study can do retreospective studies
case control
what does threshold approach mean
assuming a compound is safe below a certain concentration
what are 2 examples of threshold approaches
NOAEL and LOAEL
what does LOAEL stand for
lowest observed adverse effect level
what does NOAEL stand for
no observed adverse effect level
what is NOAEL
the highest non statistically significant dose tested (usually like 10% above background)
what is LOAEL
lowest dose tested to produce a statistically significant dose (usually like 10% above background)
what is the point of departure (definition)
point on dose response curve established rom experimental or observational data generally corresponding to an estimated low effect level or no-effect level (marks beginning of extrapolation) usually NOAEL
what does the point of departure usually signify
NOAEL
is NOAEL or LOAEL higher on the graph
LOAEL
what does it mean if a dose response curve intersects with the Y axis
there is a natural incidence of this response in the natural population
why is it hard to test for thresholds in animals
you want to test low doses, but at very low doses, chemicals rarely induce a disease state so large numbers of animals must be tested
what are 2 measurements that use NOAEL
RfD and ADI
what does RfD stand for
reference dose
what is RfD
estimates of a daily exposure to an agent that is assumed to be without adverse health impact on the human population
what is ADI
daily intake over an entire lifetime which appears to be without appreciable risk on the basis of all known facts
what is the equation for RfD
NOAEL / UF*MF
what is the equation for ADI
NOAEL / UF*MF
what is UF
uncertainty factor
what is MF
modifying factor to alter UF
what happens if you wanna calculate RfD or ADI but theres to NOAEL
use LOAEL
what is UF if data is from another species
10
what is UF if intraspecies variation
10
what is UF if data only LOAEL is available
10
what is UF if study is not chronic
10
what are 4 examples of things that would add 10s to UF
- data from another species
- intraspecies variation
- data only LOAEL is available
- study is not chronic
what do you do to MF if calculating for children
use factor of 10
what is an example of something that would change MF
if using in kids
what is RfD if 500 animals, subchronic, NOAEL=5
5/ ((1000)(0.8)) = 0.006
rats +10
variation +10
not chronic+10
good confidence cause high number MF=0.8
what does MOE stand for
margin of exposure
what is MOE
ratio of NOAEL compared to level which humans may be exposed
what # of MOE gets flagged for potential toxicity
if its under 100
what does a large MOE mean
safer, means you are far from toxic dose
what does a small MOE mean
more dangerous, closer to toxic dose
what is BMD
benchmark dose
what is the main goal of calculating BMD
use it to estimate daily oral or dermal exposure level to the human population that is likely without risk in lifetime
what is a new preferred way of figuring out reference dose
using BMD instead of NOAEL
what is BMR
benchmark response
what is BMD
a dose that produces a predetermined increase in the rate of response, BMR (you are more working backwards, find dose that gives response like 5-10%)
what are the default BMR values
5% to 10% changes in response rate of an adverse effect relative to a control group
what kind of data can be used to find BMD
quantal or continuous data
what do you need to know in order to do benchmark dose
the upper and lower confidence limits of the data points
what is the confidence limit
confidence that true value lies somewhere within that boundary of values, usually at 95%
how are BMR and BMD related
the dose at which BMR occurs is the BMD
statistically, what is the BMD
a range of values bordered by upper and lower confidence limits
what is chosen as the BMD (BMDL)
the lowest dose defined by the confidence limit
how do you calculate RfD using BMD
same, just use it instead of NOAEL
what are 4 advantages of BMD over NOAEL
- not limited to experimental dose
- less dependent on dose spacing
- compare diff chemical responses (all response levels at 10%)
- flexibility in determining biologically significant rates (if BMR is 5% and causes small increase, can be dangerous)
