ETX135 Participation Surveys + Quiz (MT)

Risk = Hazard

a) True

b) False

b) False

RISK = HAZARD x EXPOSURE

What are the major steps involved with conducting a risk assessment?

a) Data collection, hazard identification, dose-response assessment, risk characterization

b) Hazard identification, dose-response assessment, exposure assessment, risk characterization

c) Hazard identification, dose-response assessment, exposure assessment, risk management

b) Hazard identification, dose-response assessment, exposure assessment, risk characterization

Hazard identification involves:

a) Determining the dose-response relationship

b) Identifying the exposure pathway

c) Identifying all kinds of chemicals that might affect the health of a community

d) Determining whether there is evidence that exposure to a particular chemical can cause adverse health effects, and if so, identifying the specific health effects (e.g., cancer) associated with exposure to the chemical

d) Determining whether there is evidence that exposure to a particular chemical can cause adverse health effects, and if so, identifying the specific health effects (e.g., cancer) associated with exposure to the chemical

Hazard Identification is a process that relies only on animal data

a) True

b) False

b) False

IARC is one entity that formally identifies carcinogens. As regards how IARC classifies the evidence relevant to carcinogenicity from studies in humans, match two of these classification terms to the appropriate definition:

a) Limited Evidence of Carcinogenicity

b) Inadequate Evidence Regarding Carcinogenicity

Definitions…

1) “A causal interpretation of the positive association observed in the body of evidence on exposure to the agent and cancer is credible, but chance, bias, or confounding could not be ruled out with reasonable confidence”

2) “The available studies are of insufficient quality, consistency, or statistical precision to permit a conclusion to be drawn about the presence or the absence of a causal association between exposure and cancer, or no data on cancer in humans are available”

a) = 1)

b) = 2)

IARC is one entity that formally identifies carcinogens. As regards how IARC classifies an agent as probably carcinogenic to humans (Group 2A), the Working Group must have made a determination that there is limited evidence of carcinogenicity in humans, not just in human cells or tissues.

a) True

b) False

b) False

The Group 2A category generally applies when the Working Group has made at least two of the following evaluations, including at least one that involves either exposed humans or human cells or tissues:

• Limited evidence of carcinogenicity in humans

• Sufficient evidence of carcinogenicity in experimental animals

• Strong evidence that the agent exhibits key characteristics of carcinogens

Which of the following is NOT an advantage of use of long-term animal studies for evaluation of cancer?

a) Controlled experiments reduce many sources of bias and confounding

b) Ability to administer high doses increases power to detect an effect

c) Two-year study duration in rodents - you get results much sooner than from epidemiological studies

d) Large historical database on spontaneous occurrence / animal’s physiology generally well-characterized

e) All of these are advantages

e) All of these are advantages

At low doses there will be no response to a toxicant

a) True

b) False

b) False

As with hazard identification, there is frequently a lack of dose-response data available for human subjects. Also, as with hazard identification, animal studies are frequently done to augment the available data.

Use of animal studies can introduce uncertainty into the dose-response analysis in which of the following way(s)? [select all that apply]

a) Dose-response relationships observed from animal studies are often at much higher doses that would be anticipated for humans, so must be extrapolated to lower doses

b) Animal studies must also be extrapolated from that animal species to humans in order to predict the relationship for humans

c) Dose-response relationships observed from animal studies are often at much lower doses that would be anticipated for humans, so must be extrapolated to higher doses

a) Dose-response relationships observed from animal studies are often at much higher doses that would be anticipated for humans, so must be extrapolated to lower doses

b) Animal studies must also be extrapolated from that animal species to humans in order to predict the relationship for humans

In dose-response, the __________ effect for risk assessment is the adverse effect (or response that leads to an adverse effect) that occurs at the lowest dose across all relevant available studies

critical effect

Which of the following are true about cancer dose-response? [select all that apply]

a) Cancer endpoint is quantal (you either have it or you don’t)

b) Cancer is not randomly distributed amongst exposed individuals

c) Cancer is typically seen only many years after exposure

a) Cancer endpoint is quantal (you either have it or you don’t)

c) Cancer is typically seen only many years after exposure

Like non-cancer dose-response, cancer dose-response also typically assumes a threshold below which an effect is not expected to occur

a) True

b) False

b) False

There is NO threshold considered for such carcinogens

In a risk assessment, we must make assumptions in order to estimate human exposure to a chemical, such as the amount of time individuals spend in certain environment

a) True

b) False

a) True

When does “exposure” occur?

a) When a chemical is metabolized in the body

b) When a chemical comes in contact with a boundary such as the skin

c) When a chemical or agent pollutes an environmental medium

b) When a chemical comes in contact with a boundary such as the skin

Quantifying Exposure. There are three basic approaches for quantifying exposure. Each approach is based on different data, and has different strengths and weaknesses; using the approaches in combination can greatly strengthen the credibility of an exposure risk assessment. Match the approach to the definition.

a) Point of Contact Measurement

b) Scenario Evaluation

c) Reconstruction

Defintions:

1) “The exposure can be estimated by separately evaluating the exposure concentration and the time of contact, then combining this information”

2) The exposure can be estimated from dose, which in turn can be reconstructed through internal indicators (biomarkers, body burden, excretion levels, etc.) after the exposure has taken place

3) The exposure can be measured at the point of contact (the outer boundary of the body) while it is taking place, measuring both exposure concentration and time of contact, then integrating them

a = 3

b = 1

c = 2

A major component of exposure assessment involves:

a) Calculating an acceptable risk level

b) Determining the dose-response relationship

c) Identifying the exposure pathways

d) Determining toxicity of metabolites formed in the body

c) Identifying the exposure pathways

Which of the following is the best example of a complete exposure pathway?

a) Inhalation of PAHs (polycyclic aromatic hydrocarbons)

b) Dermal contact with organophosphate pesticides

c) Release of trichloroethylene from a manufacturing facility followed by its entry into the municipal water supply and consumption by those receiving drinking water from municipal water lines

d) Living near a hazardous waste dump

c) Release of trichloroethylene from a manufacturing facility followed by its entry into the municipal water supply and consumption by those receiving drinking water from municipal water lines

A complete exposure pathway has 5 parts

1) Source of Exposure

2) Environmental Media and Transport Mechanism

3) Point of Exposure

4) Route of Exposure

5) Receptor

The Office of Environmental Health Hazard Assessment (OEHHA) develops Reference Exposure Levels (RELs), which are __________ at or below which no adverse health impacts are anticipated following exposure for specified periods

Concentrations of a chemical in air (airborne chemicals)

A Reference Exposure Level is calculated using the following generic equation:

REL = [(POD)x(Dose Adj.)x(Time Adj.)]/[UFs]

a) True

b) False

a) True

In considering exposure duration for development of a REL, match these exposure duration to the most appropriate scenario:

a) Chronic: long-term low level for continual chronic exposures (24/7)

b) Acute: short-term higher level

Scenario:

1) For assessing exposure in residential neighborhoods

2) For assessing occasional or intermittent exposure

a = 1

b = 2

A risk characterization conveys the risk assessor’s judgment as to the risks that are expected to occur in the exposed population, along with information about how the risk was assessed, where assumptions and uncertainties still exist.

a) True

b) False

a) True

Noncancer risk is usually determined by comparing the actual level of exposure to a chemical to the level of exposure that is not expected to cause any adverse effects, even in the most susceptible people. The levels of exposure at which no adverse health effects are expected are generally called __________.

Health Reference Levels

Cancer risk is often expressed as the maximum number of new cases of cancer projected to occur in a population of one million people due to exposure to the cancer-causing substance over a lifetime.

a) True

b) False

a) True

What is pesticide residue? What is pesticide tolerance? [Matching]

a) Pesticide residue

b) Pesticide tolerance

Definitions:

1) Maximum legally allowed residue concentration for a pesticide on a commodity

2) Actual amount (concentration) of pesticide detected on a commodity

a = 2

b = 1

What are “illegal” pesticide residues? [select all that apply]

a) Residue over tolerance, or Pesticide residue > tolerance for that pesticide on the commodity sampled

b) Residue on a commodity with “NTE” or no tolerance established

c) Residues on imported produce

d) Residues above a laboratory limit of detection

a) Residue over tolerance, or Pesticide residue > tolerance for that pesticide on the commodity sampled

b) Residue on a commodity with “NTE” or no tolerance established

Matching - Agency Roles

a) CDPH

b) OEHHA

c) CDFW

1) Implements fishery closures and reopenings

2) Evaluates health risks and recommends oil-spill fishery closures and reopenings

3) Consults with OEHHA concerning domoic acid fishery recommendations

a = 3

b = 2

c = 1

Why is the persistent-contaminant fish advisory model difficult to apply to cyanotoxins?

a) Cyanotoxin conditions can change rapidly across time and location

b) Cyanotoxin occur at identical concentrations throughout a lake

c) All cyanotoxins disappear immediately after a bloom

d) Cyanotoxins affect water but cannot expose aquatic organisms

a) Cyanotoxin conditions can change rapidly across time and location

When multiple contaminants affect advice for a particular fish and population group, which contaminant drives the recommendation?

a) The contaminant detected at the highest concentration

b) The contaminant with the longest chemical name

c) The contaminant measured by the most sensitive laboratory method

d) The contaminant resulting in the lowest recommended number of servings

d) The contaminant resulting in the lowest recommended number of servings

The target excess lifetime cancer risk used to develop the oil-spill PAH level of concern in the lecture was?

a) 10^-2

b) 10^-4

c) 10^-6

d) 10^-5

d) 10^-5

In risk characterization, cancer risk is often expressed as the maximum number of new cases of cancer projected to occur in a population (e.g., 2 excess cases in 100,000 or 1,000,000 people so exposed) due to exposure to the cancer-causing substance over a lifetime.

a) True

b) False

a) True

Toxicokinetics can be thought of as how the chemical interacts with receptors in the body (i.e., mechanism of action for target effects)

a) True

b) False

b) False

In determining a human cancer potency, you have the following information from a BMD model of data from an appropriate study in female rats: BMDL of 10 ppb and a BMR of 0.1, which you use to calculate the animal cancer potency (hint: cancer potency = 1 = slope factor). Remembering that you also have to apply an interspecies scaling conversion factor (~4 for rats, ~7 for mice)…your human cancer potency (qh) would be best expressed as:

a) qhuman = (0.1/10ppb) x 7

b) qhuman = (10ppb/0.1) x 4

c) qhuman = (0.1/10ppb) / 7

d) qhuman = (0.1/10ppb) / 4

e) qhuman = (0.1/10ppb) x 4

f) qhuman = (10ppb/0.1) / 4

e) qhuman = (0.1/10ppb) x 4

In conducting a cancer risk assessment under either OEHHA/US EPA frameworks, you would apply a/an [Blank 1] to calculate cancer risk for segments of the lifespan to account for increased sensitivity to carcinogens in [Blank 2]. Select the best fitting term.

Blank 1

a) Uncertainty Factor

b) Heterogeneous populations

c) Early pregnancy

d) Age-weighted factor

e) Age-sensitivity factor

f) Early life stages

Blank 2

a) Early stage of pregnancy only

b) Uncertainty Factor

c) Heterogenenous populations

d) Age-sensitivity factor

e) Early life stages

f) Age-weighted factor

Blank 1

e) Age-sensitivity factor

Blank 2

e) Early life stages

Upon considering all available studies, the adverse effect, or a measure of response that leads to an adverse effect (known as a ‘precursor’ to the effect), that occurs at the lowest dose is selected as the critical effect for risk assessment. The underlying assumption is that if the critical effect is prevented from occurring, then no other effects of concern will occur.

a) True

b) False

a) True

We can deem an “upstream” measure of response that leads to an adverse effect a critical effect, as if we prevent the precursor, we prevent the “downstream” effects as well.

In calculating a Reference Exposure Level (REL), availability of a Human Equivalent Concentration in lieu of DAF derived from a robust PBPK model can also be considered sufficient to justify some reduction in the value applied for intRAspecies uncertainty, specifically the portion contributed by toxicokinetic differences.

a) True

b) False

b) False

A HEC is reducing the toxicokinetics contribution to interspecies UF

Which of the following would constitute “other relevant data” that IARC might use to indicate a chemical is a carcinogen? [select all that apply]

a) Evidence that the chemical decreases immune surveillance

b) There is evidence the chemical is genotoxic

c) Mechanistic data shows that the chemical acts on receptors like other known carcinogens

a) Evidence that the chemical decreases immune surveillance

b) There is evidence the chemical is genotoxic

c) Mechanistic data shows that the chemical acts on receptors like other known carcinogens

Noncancer risk is usually determined by comparing the actual level of exposure to a chemical to the level of exposure that is not expected to cause any adverse effects in a general population (i.e., not the most susceptible people)

a) True

b) False

b) False

In calculating a noncancer Hazard Index (HI) for a scenario involving multiple chemicals, hazard quotients can be summed across chemicals, for example, to separately estimate acute HI, chronic HI, for each relevant target organ/organ system.

a) True

b) False

a) True

In calculating a Reference Concentration for a toxicant found in air, US EPA is setting a concentration of chemical in air that is not anticipated to result in adverse noncancer health effects (including sensitive subpopulations)

a) True

b) False

a) True

BMD modeling for cancer is similar to BMD modeling for non-cancer in that there are many potentially acceptable model options that can be used and we choose the best fit.

a) True

b) False

b) False

We only use best fit in noncancer BMDS

In a risk assessment, we must make assumptions in order to estimate human exposure to a chemical, such as the amount of time individuals spend in a certain environment

a) True

b) False

a) True

IARC is one entity that formally identifies carcinogens. Limited evidence of carcinogenicity in humans is not required for IARC to classify an agent as probably carcinogenic to humans (Group 2A). Classification may instead be based on sufficient evidence of carcinogenicity in experimental animals AND strong evidence that the same mechanism operates in humans.

a) True

b) False

a) True

As with hazard identification, there is frequently a lack of dose-response data available for human subjects. Also, as with hazard identification, animal studies are frequently done to augment the available data. Use of animal studies can introduce uncertainty into the dose-response analysis in which of the following way(s)? [select all that apply]

a) Dose-response relationships observed from animal studies are often at much higher doses that would be anticipated for humans, so must be extrapolated to lower doses

b) Dose-response relationships observed from animal studies are often at much lower doses that would be anticipated for humans, so must be extrapolated to higher doses

c) Animal studies must also be extrapolated from that animal species to humans in order to predict the relationship for humans

a) Dose-response relationships observed from animal studies are often at much higher doses that would be anticipated for humans, so must be extrapolated to lower doses

c) Animal studies must also be extrapolated from that animal species to humans in order to predict the relationship for humans

A major component of exposure assessment involves:

a) Determining toxicity of metabolites formed in the body

b) Identifying the exposure pathways

c) Calculating an acceptable risk level

d) Selecting an appropriate animal study

e) Determining the dose-response relationship

b) Identifying the exposure pathways

In the context of human health risk assessment, when does “exposure” occur?

a) When a chemical comes in contact with a boundary such as the skin

b) When a chemical is metabolized in the body

c) When a chemical or agent pollutes an environmental medium

d) When a chemical can be measured leaving a source

a) When a chemical comes in contact with a boundary such as the skin

Which of the following reasons are why risk assessors prefer the BMDL as a better point of departure over the NOAEL or LOAEL? [select all that apply]

a) The assessor knows that they can calculate a BMDL in any data set (even if there is no NOAEL)

b) If you have a number of possible data sets from different studies to use, you can get a better handle on what endpoint is most sensitive using the BMDL compared to the NOAEL approach

c) The BMDL accounts for some of the uncertainty in the experimental data because it includes the sample size in the curve fitting, and is the 95% lower confidence limit on the dose producing a specified response rate

d) The assessor knows where the BMDL lies on the dose-response curve more accurately than the NOAEL because they set the response rate when running the model

b) If you have a number of possible data sets from different studies to use, you can get a better handle on what endpoint is most sensitive using the BMDL compared to the NOAEL approach

c) The BMDL accounts for some of the uncertainty in the experimental data because it includes the sample size in the curve fitting, and is the 95% lower confidence limit on the dose producing a specified response rate

d) The assessor knows where the BMDL lies on the dose-response curve more accurately than the NOAEL because they set the response rate when running the model

In risk assessment, it is typically assumed that there is a threshold for cancer toxicity. In other words, it is generally assumed that there is a “safe” level of exposure at or below which no effect is anticipated.

a) True

b) False

b) False