Risk Management Quiz 1 + 2

Front 1

Additional Risk

Back 1

Additional proportion of population that respond given conditional exposure

Front 2

ADI

Back 2

Allowable Daily Intake. Concentration of certain substance that can be taken, generally for a lifetime, and not show any adverse effects.

Front 3

adverse

Back 3

contrary to ones interests or welfare

Front 4

Adverse Effect

Back 4

Biochemical change or impairment that may affect well being of organism and its fitness

Front 5

allometry

Back 5

The study of natural human anatomical and physiological variation

Front 6

Benchmark Dose

Back 6

An exposure level that corresponds to a statistical lower confidence limit on the dose producing a predetermined response.

Front 7

Bright Line:

Back 7

specific value or line drawn as a boundary to separate acceptable vs unacceptable risk

Front 8

Central Tendency

Back 8

Descriptive term about accessing risk or groups that refers to mean, median.

Front 9

Cancer Potency Factor

Back 9

See Risk Factor

Front 10

Critical Effect:

Back 10

First adverse effect at the lowest exposure level; first adverse effect as dose increases.

Front 11

Effect

Back 11

response to a stimulus, outcome.

Front 12

Excess Risk/Extra Risk

Back 12

total proportion of additional risk responses caused by exposure that would not have that predetermined response.

total additional proportion of response compared to background proportion caused by exposure.

Front 13

Extrapolation

Back 13

Through regression or other means, estimating a data point outside of our range of experimental values.

Front 14

Hazard Quotient

Back 14

The ratio of the dose resulting from exposure to an agent and the chemical’s reference dose (RfD) or other screening benchmark.

Front 15

Health

Back 15

State of an organism with respect to functioning, disease, and abnormality at any given time.

Front 16

Health Effect:

Back 16

Functional or structural response affecting the organism, but not necessarily leading to impairment or reduced capacity

Front 17

Interpolation

Back 17

Estimation of responses within the range of experimental data; determination of intermediate values in a series on the basis of observed values.

Front 18

LOAEL

Back 18

lowest observed adverse effect level. Lowest experimentally determined dose where a biologically or statistically significant adverse effect (critical effect) occurs compared to control

Front 19

LOEL

Back 19

lowest observed adverse effect level. Lowest experimentally determined dose where a biologically or statistically significant effect occurs compared to control

Front 20

MOE

Back 20

Margin of Exposure. Ratio of NOAEL to the current estimated exposure dose of interest.

Front 21

MOS

Back 21

See Margin of Exposure

Front 22

Mechanism of Action

Back 22

Specific details of the biological processes (e.g., at the
molecular level) by which an agent causes its effects.

Front 23

Mode of Action:

Back 23

Series of key events involving interaction with cells, leading to operational or anatomic changes, resulting in disease; an incomplete aspect of “Mechanism of Action”.

Front 24

NOAEL

Back 24

“No Observed Adverse Effect Level”: An experimentally determined dose at which no statistically or biologically significant indications of toxic effects (critical effect) are observed beyond those seen in a control group.

Front 25

NOEL

Back 25

“No Observed Effect Level”: Highest experimentally determined dose at which no statistically or biologically significant effects are observed beyond those seen in a control group.

Front 26

Pharmacodynamics

Back 26

The study through measurement or modeling of the response of a biological system as a function of dose. Referred to as: “The linkage between dose and response” (NRC '94).

Front 27

Pharmacokinetics

Back 27

The study through measurement or modeling of the absorption, distribution, metabolism, and excretion of drugs or chemicals in a biological system as a function of time. Referred to as: “The linkage between exposure and dose” (NRC '94).

Front 28

Point of Departure

Back 28

The dose-response point that marks the beginning of a low-dose extrapolation. This point can be the lower bound on dose for an estimated incidence or a change in response level from a dose-response model (BMD), or a NOAEL or LOAEL for an observed incidence, or change in level of response.

Front 29

Potency Factor:

Back 29

Risk Factor

Front 30

Q1*:

Back 30

The upper bound on the cancer potency factor for low-dose exposures as calculated using the linearized multistage (LMS) model.

Front 31

Residual Risk

Back 31

That risk which remains after risk reduction actions have been implemented.

Front 32

RfC

Back 32

“Reference Concentration”: An estimate (with uncertainty spanning perhaps an order of magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups) that is likely to be without appreciable risk of adverse effects during a lifetime.

Front 33

RfD

Back 33

“Reference Dose”: An estimate (with uncertainty spanning perhaps an order of magnitude) of a daily exposure to the human population (including sensitive subgroups) that is likely to be without appreciable risk of adverse effects during a lifetime.

Front 34

Risk

Back 34

Probability of a specific, generally adverse outcome (e.g., injury, disease or death) given a particular set of conditions (e.g., exposure dose and route of exposure) and relative to the background probability.

Front 35

Risk Assessment

Back 35

Scientific activity of evaluating the toxic properties of a chemical and the conditions of human exposure to it in order to ascertain the likelihood that exposed humans will be adversely affected and to characterize the nature of the effects they may experience.

Front 36

Slope Factor

Back 36

Excess risk per unit of dose at a specific dose. Also referred to as the “Slope Factor” or “Potency Factor”.

Front 37

Susceptibility

Back 37

How much additional risk of an adverse outcome that can be attributed to some variable or exposure

Front 38

Threshold

Back 38

The line that separates adverse health effects and below no adverse outcomes are likely to occur.

Front 39

Ultimate Toxicant

Back 39

the final form of a toxicant that interacts on a cellular level to cause toxicity to life.

Front 40

Unit Risk

Back 40

The upper bound measuring excess risk at a standard unit point of (generally continuous) exposure.

Front 41

Upper Bound

Back 41

Statistical upper confidence interval limit, used for relevant risk measurements.

Front 42

Threshold vs Non-Threshold Domains of Risk Analysis.

Back 42

Risk analysis evolved into two domains:
cancer risk assessment = non-threshold
non-cancer risk assessment = threshold

i.e. for cancer, any amount is dangerous and carcinogenic

Front 43

Threshold toxicant

Back 43

Substance known or assumed to have a threshold, below which no adverse health effects are expected; some exposure level is “safe“

Front 44

NOAEL/LOAEL Model

Back 44

One threshold Risk Assessment Model (two others)
FDA: Allowable Daily Intake (ADI)
The amount of chemical to which a person can be exposed on a daily basis over an extended period of time (usually a lifetime) without suffering an adverse effect
ADI = NOAEL / [Safety Factor]

Front 45

Tolerance Distribution Model

Back 45

One threshold Risk Assessment Model (two others)
Statistical models that characterize the population dose response variability and estimate population response thresholds


log-probit (probit)
log-logistic (logit)
Weibull (time to failure)

Front 46

Benchmark Dose Model

Back 46

One threshold Risk Assessment Model (two others)

Front 47

Inter-species Safety Factor (UFA)

Back 47

Inconsistency of mechanisms across species
Addresses uncertainty of extrapolation from animals to humans, when human data are lacking
Default = 10

Front 48

Intra-species Safety Factor (UFH)

Back 48

Variable responses between humans
Addresses uncertainty of extrapolation from general population to susceptible sub-groups
Default = 10

Front 49

LOAEL to NOAEL Adjustment Factor (UFL)

Back 49

Inappropriateness of experimental end-point
Addresses uncertainty from using a LOAEL when NOAEL data are lacking
Default = 10

Front 50

Exposure Duration Adjustment Factor (UFD)

Back 50

Inappropriateness of exposure duration
Addresses uncertainty from using sub-chronic data when chronic exposure data are lacking
Default = 10

Front 51

Sources of Uncertainty

Back 51

Insufficient experimental data

Inconsistent experimental data

Limited distribution or range of data

Humans differ from experimental animals: Differing pharmacokinetics, Differing pharmacodynamics

Humans differ among themselves

Differing susceptibility

Heterogeneity (genetic, lifestyle, etc.)

Parameter uncertainty and variability:measurement error, random error, systematic error

Model uncertainty: surrogate and excluded variables, incorrect model

Decision-rule uncertainty

Front 52

NOAEL/LOAEL (safety factor) Model Advantages and Disadvantages (name at least three)

Back 52

Advantages: Relative simplicity and Ease of application

Disadvantages:
-Underutilization of available data. NOAEL is limited to tested data. Only one data point is considered.
-Shape of dose response curve is ignored.
-Size of study population is (usually) ignored
-Reference Dose (rfD): indicates who is at risk not the size of the risk.
-RfD biased statistic. UF conservative so RfD biased down.
-Difficulties in interspecies scaling.

Front 53

EDn and ECn
LDn and LCn

Back 53

Critical effects for tolerance distribution model.
EDn and ECn are for dose and cxn causing a specific effect in (n% of pop)

LDn and LCn are for dose and cxn causing a LETHAL effect in (n% of pop)

Front 54

Tolerance Distribution Model Steps

Back 54

Find appropriate empirical dose-response data

Select a mathematical function that describes the empirical dose-response data.

Calculate the goodness-of-fit

Set a critical effect threshold

Front 55

Weight of Evidence

Back 55

“Collective evaluation of all pertinent information so that the full impact of biological plausibility and coherence are adequately considered”
Considerations include: quality and quantity of data
ability to detect effects (sensitivity), consistency of results across studies, biological plausibility

Front 56

Carcinogenicity Cancer Risk Assessment

Back 56

Group 1: Definitely so
Group 2: Maybe so.
3: not classifiable, inadequate proof
4: Agent no carcinogenic.

Front 57

weight of evidence

Back 57

Weight of Evidence

“Collective evaluation of all pertinent information so that the full impact of biological plausibility and coherence are adequately considered”

EPA and IARC have different forms of measuring