PUBH 6011 Final GW LaPuma Exam Questions
And Answers Verified 100% Correct
Define NOAEL, LOAEL, LD50, LC50, RfD, CSF, benchmark dose - ANSWER -
NOAEL (No Observed Adverse Effect Level) is the highest dose administered that
does not produce a statistically significant increase in an adverse effect
LOAEL (Low Observed Adverse Effect Level) is the lowest dose tested that
produces a statistically significant increase in an adverse effect
Threshold is the dose at which the most sensitive members in a population begin to
respond. Below threshold, there are no adverse effects.
LD50 is the dose (mg/kg) lethal to 50% of the population
LC50 is the concentration (in ppm or mass/volume) lethal to 50% of the population
Reference dose (RfD) is a level of daily oral exposure to a chemical, such as a
pesticide, that has no apparent adverse effect on humans; the RfD is used in setting
regulatory guidelines
Cancer slope factor (CSF) is an estimate of an increase in cancer risk per
mg/kg/day of average daily dose (ADD); combined with an estimate of exposure to
create an upper bound on increased cancer risk from an exposure
Benchmark dose is a dose or concentration that produces a predetermined change
in response rate of an adverse effect
Differentiate between acute and chronic toxicity - ANSWER -Acute toxicity is the
sudden onset of toxic effect (hours or days), usually from a single dose, often
reversible. Involves rapid effects which can include death, CNS effects, GI tract,
lung, skin, etc.
Chronic toxicity is a toxic effect seen after long term exposure (years). Examples
include cancer, liver damage, lung fibrosis, etc. Results of prolonged exposure
usually in lower doses than acute.
Describe absorption, distribution, metabolism, and excretion - ANSWER -
Absorption is the ability for a chemical to cross a cellular membrane and to enter
the body. There are three ways to cross the phospholipid bilayer. Passive diffusion
is the transfer across the membrane with no energy needed (follows the
concentration gradient). The three key determinants are size (smaller gets in
,easier), hydrophobicity (more hydrophobic goes through easier), and ionization
(charge). Facilitated diffusion works via protein channels and carrier proteins. This
allows selective movement of molecules in and out of cell membranes and still
works along concentration gradients. Active transport requires ATP to move
molecules across the membrane; usually the transport is against the concentration
gradient. Requires proteins for certain molecules.
Distribution is the way certain compounds are distributed throughout the body and
their propensity to build up in certain tissues or organs. Most distribution occurs
through the blood and lymphatic system. As blood passes through organs and
tissue, chemicals may be transferred (depends on properties of the organ and the
chemical, so not all organs and tissues have the same concentration of a chemical)
Metabolism is the enzymatic alteration of the chemical structure of a molecule.
Makes molecules easier to excrete. Phase 1 is a family of enzymes that can react
with many different chemicals; it adds polar groups (making chemical more water
soluble) or reactive groups (setting up for phase 2 reactions) to the substrate. These
are inducible reactions which means that an exposure to the substrate can increase
production of the enzyme. Phase 2 uses conjugation reactions to make molecules
bigger by adding on other large molecules to increase biliary or urinary excretion.
Also inducible.
Excretion removes molecules from the body. Routes include kidney/urinary tract,
bile/fec
Characterize the primary routes of human exposure - ANSWER -Oral/ingestion is
the introduction of a compound into the digestive tract via the mouth
Inhalation is the introduction of a gas or particle into the lungs via the airway
Dermal is the process by which a chemical gains entry into the body via the skin
Four steps of environmental risk assessment - ANSWER -Hazard identification is
used to identify what health problems are caused by the pollutant. It asks the
questions: what harmful effects is the agent capable of causing? At what dose are
the effects seen? Is there additional information that can help us understand the
hazard posed by the agent?
Dose-Response Evaluation is used to identify what the health effects are at
different levels of exposure and how much of the chemical does it take for an
adverse effect to occur.
, Exposure Assessment examines how much of the pollutant are people exposed to
during the day and looks at how many people are exposed. Asks: how much of a
substance are people exposed to? What are the sources of exposure? What are the
pathways of exposure?
Risk Characterization examines the extra risk of a health problem in the exposed
population and estimates the magnitude of risk
Difference in risk assessment logic for carcinogens and non-carcinogens -
ANSWER -Risk assessment assess the nature and magnitude of the risk. Cancer
has no threshold, noncancer has a threshold before which no adverse responses are
seen. The best model for cancer research is animal testing because we do not dose
humans (bacterial testing (in vitro), 14 day acute (noncancer), 90 day chronic
(noncancer), 2 year chronic (cancer). Maximally Tolerated Dose (MTD) is used in
cancer studies and is the highest dose you can give an animal before it dies.
Cancer environment risk can be found by using dose x slope factor; y=mx. RfD <
NOAEL < LOAEL. The distance between the RfD and NOAEL is the uncertainty
factor.
The uncertainty factor (safety factor) is an approach for noncarcinogens that
assumes a threshold due to short latency, reversible lesions depending on the dose,
severity being dependent on the dose, and is caused by collective effect on many
cells.
Probabilistic modeling for carcinogens assumes no threshold due to long latency,
irreversible lesions becoming independent of dose, auto-amplifying (all or none),
and small rare events in a single cell
Interpret hazard severity based on cancer slopes and RfDs - ANSWER -Hazard
quotient is a noncancer risk assessment and it uses exposure/RfD.
RfD is the reference dose, an estimate of daily exposure to population that is likely
to be without an appreciable risk of deleterious effects during a lifetime. An
exposure below RfD is without appreciable risk.
Carcinogen risk assessment is the risk from a lifetime exposure (individual lifetime
risk). This is an incremental increase in the probability of cancer, usually by a
factor of 10. EPA aims for risk below 1 in a million. Exposure x Cancer Slope
Factor
And Answers Verified 100% Correct
Define NOAEL, LOAEL, LD50, LC50, RfD, CSF, benchmark dose - ANSWER -
NOAEL (No Observed Adverse Effect Level) is the highest dose administered that
does not produce a statistically significant increase in an adverse effect
LOAEL (Low Observed Adverse Effect Level) is the lowest dose tested that
produces a statistically significant increase in an adverse effect
Threshold is the dose at which the most sensitive members in a population begin to
respond. Below threshold, there are no adverse effects.
LD50 is the dose (mg/kg) lethal to 50% of the population
LC50 is the concentration (in ppm or mass/volume) lethal to 50% of the population
Reference dose (RfD) is a level of daily oral exposure to a chemical, such as a
pesticide, that has no apparent adverse effect on humans; the RfD is used in setting
regulatory guidelines
Cancer slope factor (CSF) is an estimate of an increase in cancer risk per
mg/kg/day of average daily dose (ADD); combined with an estimate of exposure to
create an upper bound on increased cancer risk from an exposure
Benchmark dose is a dose or concentration that produces a predetermined change
in response rate of an adverse effect
Differentiate between acute and chronic toxicity - ANSWER -Acute toxicity is the
sudden onset of toxic effect (hours or days), usually from a single dose, often
reversible. Involves rapid effects which can include death, CNS effects, GI tract,
lung, skin, etc.
Chronic toxicity is a toxic effect seen after long term exposure (years). Examples
include cancer, liver damage, lung fibrosis, etc. Results of prolonged exposure
usually in lower doses than acute.
Describe absorption, distribution, metabolism, and excretion - ANSWER -
Absorption is the ability for a chemical to cross a cellular membrane and to enter
the body. There are three ways to cross the phospholipid bilayer. Passive diffusion
is the transfer across the membrane with no energy needed (follows the
concentration gradient). The three key determinants are size (smaller gets in
,easier), hydrophobicity (more hydrophobic goes through easier), and ionization
(charge). Facilitated diffusion works via protein channels and carrier proteins. This
allows selective movement of molecules in and out of cell membranes and still
works along concentration gradients. Active transport requires ATP to move
molecules across the membrane; usually the transport is against the concentration
gradient. Requires proteins for certain molecules.
Distribution is the way certain compounds are distributed throughout the body and
their propensity to build up in certain tissues or organs. Most distribution occurs
through the blood and lymphatic system. As blood passes through organs and
tissue, chemicals may be transferred (depends on properties of the organ and the
chemical, so not all organs and tissues have the same concentration of a chemical)
Metabolism is the enzymatic alteration of the chemical structure of a molecule.
Makes molecules easier to excrete. Phase 1 is a family of enzymes that can react
with many different chemicals; it adds polar groups (making chemical more water
soluble) or reactive groups (setting up for phase 2 reactions) to the substrate. These
are inducible reactions which means that an exposure to the substrate can increase
production of the enzyme. Phase 2 uses conjugation reactions to make molecules
bigger by adding on other large molecules to increase biliary or urinary excretion.
Also inducible.
Excretion removes molecules from the body. Routes include kidney/urinary tract,
bile/fec
Characterize the primary routes of human exposure - ANSWER -Oral/ingestion is
the introduction of a compound into the digestive tract via the mouth
Inhalation is the introduction of a gas or particle into the lungs via the airway
Dermal is the process by which a chemical gains entry into the body via the skin
Four steps of environmental risk assessment - ANSWER -Hazard identification is
used to identify what health problems are caused by the pollutant. It asks the
questions: what harmful effects is the agent capable of causing? At what dose are
the effects seen? Is there additional information that can help us understand the
hazard posed by the agent?
Dose-Response Evaluation is used to identify what the health effects are at
different levels of exposure and how much of the chemical does it take for an
adverse effect to occur.
, Exposure Assessment examines how much of the pollutant are people exposed to
during the day and looks at how many people are exposed. Asks: how much of a
substance are people exposed to? What are the sources of exposure? What are the
pathways of exposure?
Risk Characterization examines the extra risk of a health problem in the exposed
population and estimates the magnitude of risk
Difference in risk assessment logic for carcinogens and non-carcinogens -
ANSWER -Risk assessment assess the nature and magnitude of the risk. Cancer
has no threshold, noncancer has a threshold before which no adverse responses are
seen. The best model for cancer research is animal testing because we do not dose
humans (bacterial testing (in vitro), 14 day acute (noncancer), 90 day chronic
(noncancer), 2 year chronic (cancer). Maximally Tolerated Dose (MTD) is used in
cancer studies and is the highest dose you can give an animal before it dies.
Cancer environment risk can be found by using dose x slope factor; y=mx. RfD <
NOAEL < LOAEL. The distance between the RfD and NOAEL is the uncertainty
factor.
The uncertainty factor (safety factor) is an approach for noncarcinogens that
assumes a threshold due to short latency, reversible lesions depending on the dose,
severity being dependent on the dose, and is caused by collective effect on many
cells.
Probabilistic modeling for carcinogens assumes no threshold due to long latency,
irreversible lesions becoming independent of dose, auto-amplifying (all or none),
and small rare events in a single cell
Interpret hazard severity based on cancer slopes and RfDs - ANSWER -Hazard
quotient is a noncancer risk assessment and it uses exposure/RfD.
RfD is the reference dose, an estimate of daily exposure to population that is likely
to be without an appreciable risk of deleterious effects during a lifetime. An
exposure below RfD is without appreciable risk.
Carcinogen risk assessment is the risk from a lifetime exposure (individual lifetime
risk). This is an incremental increase in the probability of cancer, usually by a
factor of 10. EPA aims for risk below 1 in a million. Exposure x Cancer Slope
Factor
