Risk Assessment (17-18) Flashcards
Risk:
the likelihood of an adverse health effect resulting from exposure to a potential hazard (e.g. a toxic chemical)
Hazard:
any source of potential adverse health effects
Human Health Risk Assessment:
the process to estimate the nature, probability, and magnitude of adverse health effects in humans who may be exposed to chemicals in contaminated environmental media
**The 4 steps of the risk assessment process:
be able to quickly describe each
hazard identification –> dose-response assessment, exposure assessment –> risk characterization
4 methods of hazard identification:
- structure-activity relationships
- in-vitro and short-term tests
- animal bioassays
- epidemiological data
NOEL:
no-observed-effect-level; the highest exposure among all the available experimental studies at which no toxic effect was observed
NOAEL:
no-observed-adverse-effect-level; the highest exposure at which there is no statistically or biologically significant increase in the frequency of an adverse effect when compared with a control group
LOAEL:
lowest-observed-adverse-effect-level
**mechanism of action:
a detailed understanding at the molecular level of all the steps involved in the carcinogenic process for a chemical
**mode of action:
a general description of the manner in which a chemical might act to produce its effect
**weight of evidence evaluation:
comprehensive, integrated judgment of all relevant information supporting conclusions regarding a toxicological effect
How would a dose-response curve with no threshold appear?
The line goes straight to the origin (threshold implies that there’s a safe value)
With carcinogens, we talk about _____ instead of safe values?
acceptable risk
threshold:
the dose below which no additional increase in response is observed
**Point of departure (POD):
used to specify the estimated dose near the lower end of the observed dose range, below which extrapolation to lower exposures is necessary
RDA
recommended daily allowance
ADI
acceptable daily intake
**RfD
reference dose
**RfC
reference concentration
MRL
minimal risk level
**Reference dose:
an estimate (with uncertainty spanning perhaps an order of magnitude) of daily exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime
**Reference dose formula
RfD = POD/UF (point of departure/uncertainty factors)
Uncertainty factors:
necessary reductions in the dose to account for missing data
**Cancer slope factor (SF)
derived using the upper bound estimate for risk; true risk to humans is probably unknowable, but is not likely to exceed the upper-bound estimate
**Calculation of individual cancer risk:
compare daily exposure with cancer potency factor
Lifetime Risk = Exposure x CPF
**Cancer risks of less than… are considered negligible, and greater than…. are considered significant
1/1 million; 1/10,000
**Exposure assessment approaches:
direct measurement, exposure scenario modeling, biomonitoring
**Risk Assessment:
systematic process of hazard identification, exposure assessments, dose responses, and risk characterization
Risk Characterization:
last step of risk assessment; includes not just the number of risks but the characterization of the risk (i.e. uncertainty in values, assumptions)
Risk communication:
process of exchanging information and opinion with the public
Typical threshold acceptable carcinogenic risk:
10^-6
Aggregate exposure:
1 chemical, multiple routes (e.g. blood lead)
Cumulative risk:
exposure to single or multiple chemicals and nonchemical stressors
**Risk characterization:
integrates components of the risk assessment and synthesizes an overall conclusion about risk that is complete, informative, and useful for decision makers
**Risk characterization policy:
a transparent process and products that are clear, consistent, and reasonable
**Risk characterization goals
TCCR: transparency, clarity, consistency, and reasonableness
**Hazard identification/characterization:
**“appreciate the complexity”
the process of determining whether human exposure to a toxicant could cause an increase in the incidence of an adverse health effect; generally considers toxicity from one route of exposure relevant to other routes; characterizes the nature and strength of the evidence of causation
adverse effect:
biochemical damage, functional impairment, or pathologic lesion which impairs performance and reduces the ability of an organism to respond to additional challenges
adaptive effect:
enhances an organism’s performance as a whole and/or its ability to withstand a challenge
chronic toxicity:
effects that persist over a long period of time whether or not they occur immediately or are delayed
critical effect:
the first adverse effects or their known precursors that occur as dose rate increases
compensatory effect:
maintains overall function without enhancement or significant cost (e.g. increased respiration due to metabolic acidosis)
Frank effect:
the exposure level which produces unmistakable adverse effects, such as reversible or irreversible functional impairment or mortality, at a statistically or biologically significant increase in frequency or severity between an exposed population and its appropriate control
severity:
the degree to which an effect changes and impairs the functional capacity of an organ system
Uncertainty Factor (UF):
one of several, generally 10-fold, factors used in operationally deriving the RfD from experimental data
genotoxic:
does it cause gene mutations?
variability:
range of values in quantities related to risk; general sources include exposure, potency, susceptibility
possible factors for susceptibility
- fetuses vs. children vs. adolescents vs. elderly
- women vs. men
- race or ethnicity specific factors
- pre-existing health conditions
- nutrition status
Unit Cancer Risk:
the estimate of the lifetime risk caused by each unit of exposure in the low exposure region; the upper-bound excess lifetime cancer estimated to result from continuous exposure to an agent at a concentration of 1µg/L in water or 1µg/m^3 in air
** Exposure assessment:
Purpose: to calculate the dose that an individual receives
the process of measuring or estimating the magnitude, intensity, frequency, and duration of human exposure to an agent resulting from contact with environmental media
**Number of chemicals out there vs. number in IRIS:
80-90,000
<1,000
**Four types of studies used to determine hazard:
in vitro and short-term tests, in vivo/animal bioassays, epidemiological data, structure-activity relationships
**Best kind of data?
Human epidemiological data
**The type of data that we have the most of?
animal bioassays
**Why do we have uncertainty in our dose-response curves?
Because they come from animals. Plus, we may not know the chronic effects of exposing animals to these chemicals
**Non-threshold approaches:
- Characterized by a dose-response curve that goes through the origin
- No “safe dose”
- Forms the basis of cancer assessments
- Conservative and Controversial
**Threshold approaches:
Defined as the dose below which no additional increase in response is observed.
Implies a “safe dose”
Forms the basis of non-cancer assessments
**Dose:
a daily average intake per unit of body weight
**Formula for chronic daily intake of the chemical:
CDI = (C•CR•EF•ED) / (BW•AT)
CDI: Chronic daily intake of the chemical (mg/kg-day)
C: concentration of the chemical in an exposure medium
CR: contact rate
EF: exposure frequency (e.g. days/year)
ED: exposure duration (e.g. years)
BW: body weight (kg)
AT: average time (equal to ED x 365 days/year for noncarcinogens and 70 years x 365 days/year for carcinogens)
**Formula for cancer risk
definitely know this one
Risk = CDI • CSF
CDI = Chronic daily intake of the chemical (mg/kg-day) CSF = cancer slope factor for the chemical (mg/kg-day)-1
**Formula for noncancer risk:
HQ = CDI / RfD
RfD = reference dose for the chemical for assessing non-cancer health effects (mg/kg-day)
**What we call an acceptable risk for cancer:
10^-4
