NRC Flashcards
(85 cards)
1
Q
NRC: Science and Decisions (2009)
- What is the primary purpose of risk assessment according to the Silver Book?
A. Determine precise risk estimates for academic research
B. Set legal standards
C. Evaluate risk-management options to inform decisions
D. Replace risk management
A
Answer: C. The NRC emphasized integrating risk assessment directly into decision-making by evaluating the implications of different management options.
2
Q
- Which step did the NRC add to the traditional risk assessment framework to improve decision relevance?
A. Risk communication
B. Peer review
C. Problem formulation and scoping
D. Hazard index calculation
A
Answer: C. The NRC emphasized formalizing problem formulation and scoping at the start of risk assessments.
3
Q
- What is “confirmation of utility” in the NRC’s decision framework?
A. A statistical recalculation
B. An evaluation of whether the assessment answers the intended decision question
C. A peer review meeting
D. A cost-effectiveness calculation
A
Answer: B. This step checks whether the assessment is usable for decision-making.
4
Q
- Which term best describes the difference between uncertainty and variability?
A. Both mean lack of knowledge
B. Uncertainty = lack of knowledge; Variability = natural differences
C. Variability is error
D. They are interchangeable
A
Answer: B. Uncertainty can potentially be reduced with better data; variability is inherent in populations.
5
Q
- What does the Hazard Index (HI) represent?
A. Cancer risk per unit dose
B. Probability of exposure
C. Sum of hazard quotients affecting the same endpoint
D. Weight-of-evidence descriptor
A
Answer: C. HI sums hazard quotients for substances affecting the same target.
6
Q
- Which of the following is not a weight-of-evidence descriptor in EPA’s 2005 cancer guidelines?
A. Carcinogenic to Humans
B. Suggestive Evidence
C. Possibly Carcinogenic
D. Not Likely to be Carcinogenic
A
Answer: C. “Possibly Carcinogenic” was part of older classification systems, not the 2005 system.
7
Q
- What is cumulative risk assessment?
A. Adding only air and water exposures
B. Assessing combined risks from multiple agents or stressors
C. Cancer risk across regions
D. Exposure frequency in time
A
Answer: B. Cumulative risk includes both chemical and non-chemical stressors.
8
Q
- What does the NRC recommend regarding default assumptions?
A. Always use them
B. Never use them
C. Use them transparently and replace with data when criteria are met
D. Choose randomly
A
Answer: C. NRC recommends clear criteria for using or replacing defaults.
9
Q
- Why did the NRC propose redefining RfDs as “risk-specific doses”?
A. To be consistent with cancer risk
B. To express population risk levels rather than assuming zero risk below threshold
C. To reduce safety
D. To avoid uncertainty
A
Answer: B. Risk-specific doses provide quantitative risk estimates.
10
Q
- What does “adaptive management” mean?
A. Avoid action until uncertainty is resolved
B. Set standards and walk away
C. Iteratively update decisions based on new data
D. Use only default factors
A
Answer: C. Adaptive management treats risk reduction as a flexible, learning process.
11
Q
NRC: Toxicity Testing in the 21st Century (2007)
- What was the main limitation of traditional toxicity testing according to the NRC?
A. Excessive human relevance
B. Too fast
C. Slow, expensive, reliant on animals, and lacking mechanistic insight
D. Use of computers
A
Answer: C. The current system was too slow to keep up with chemical testing demands.
12
Q
- What is the core feature of the NRC’s new toxicity testing vision?
A. More animal testing
B. High-throughput human cell-based assays and computational modeling
C. Randomized human trials
D. Repeating old studies
A
Answer: B. The vision shifts toxicity testing to human-relevant, fast, pathway-focused assays.
13
Q
- What is a “toxicity pathway”?
A. Route of exposure
B. A cellular pathway that leads to adverse effects when disrupted
C. Genetic mutation site
D. Tumor growth pathway
A
Answer: B. These are biological networks that, when sufficiently perturbed, result in toxicity.
14
Q
- What does “apical endpoint” refer to?
A. A whole-animal observable adverse effect
B. A mid-dose response
C. A receptor-ligand interaction
D. An in vitro biomarker
A
Answer: A. The NRC vision emphasizes replacing apical endpoints with pathway-level data.
15
Q
- What is high-throughput screening (HTS)?
A. High-dose animal testing
B. Rapid, automated in vitro testing across many chemicals and concentrations
C. Genetic screening of humans
D. Repeat-dose animal testing
A
Answer: B. HTS enables rapid testing of many compounds.
16
Q
- Why use human cells in the new testing paradigm?
A. They provide more human-relevant data
B. They’re cheaper
C. They mutate less
D. They are immune to toxicants
A
Answer: A. Human cells better reflect human biology.
17
Q
- What is “targeted testing”?
A. Standard battery of tests
B. Specific follow-up in vitro or in vivo studies to address unresolved questions
C. Random exposure testing
D. Epidemiologic modeling
A
Answer: B. Targeted testing is selective and informed by high-throughput results.
18
Q
- What is IVIVE?
A. In vitro to in vivo extrapolation
B. In vivo imaging verification
C. Inter-variate interaction value estimate
D. Intestinal validation in vitro evaluation
A
Answer: A. IVIVE helps relate in vitro concentrations to real-world exposures.
19
Q
- How are pharmacokinetic models used in the NRC’s paradigm?
A. Ignored
B. To predict blood or tissue concentrations in humans that match in vitro effect levels
C. To test liver damage
D. To classify pesticides
A
Answer: B. PK models enable meaningful interpretation of in vitro results.
20
Q
- What role do systems biology models play in the NRC vision?
A. Policy drafting
B. Simulate biological responses to chemical perturbations
C. Replace exposure estimates
D. Serve as default assumptions
A
Answer: B. Systems biology helps predict pathway-level effects.
21
Q
Science and Decisions (2009)
- What is meant by “risk-risk tradeoff”?
A. Reducing one risk while unintentionally increasing another
B. Trading risk credits between facilities
C. Risk being redistributed to other agencies
D. Averaging cancer and non-cancer risks
A
Answer: A. An example: reducing pesticide use may increase food spoilage risks. NRC recommends recognizing such tradeoffs during decision-making.
22
Q
- Why did NRC emphasize consistency in uncertainty analysis across risk assessment components?
A. To meet legal requirements
B. Inconsistency makes it hard to interpret total uncertainty in the final risk estimate
C. To keep modeling simpler
D. To align with international treaties
A
Answer: B. EPA often analyzes uncertainty for exposure but not dose-response (or vice versa), leading to imbalanced characterizations.
23
Q
- What is the purpose of using a “tiered approach” for uncertainty/variability analysis?
A. Ensure all assessments use the most advanced models
B. Match complexity of analysis to decision importance and data availability
C. Remove low-priority risks
D. Exclude variability when data are lacking
A
Answer: B. Tiering allows for efficient resource use and appropriate depth of analysis depending on the context.
24
Q
- Why did NRC call for a “unified dose–response approach”?
A. To reduce workload
B. To standardize cancer risk only
C. To treat cancer and non-cancer effects comparably using probabilistic models
D. Because dose-response doesn’t vary across endpoints
A
Answer: C. Unified models help quantify and compare different types of risk (e.g., asthma vs. cancer).
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30. What population subgroups did NRC specifically mention as often underrepresented in assessments?
A. Policymakers
B. Athletes
C. Children, elderly, and those with genetic susceptibilities
D. Scientists
Answer: C. These groups may be more sensitive and should be explicitly included in variability considerations.
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31. What did the NRC recommend for default factor transparency?
A. Make all defaults explicit, explain rationale, and allow for justified departures
B. Keep defaults confidential
C. Apply them uniformly with no discussion
D. Eliminate all defaults
Answer: A. Transparency and justification of defaults help build trust and scientific credibility.
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32. What’s a major challenge of cumulative risk assessment that NRC identified?
A. Integrating non-chemical stressors and social factors
B. Managing laboratory resources
C. Testing long-lived chemicals
D. Modeling only one pathway
Answer: A. Few assessments include psychosocial stress, socioeconomic status, or combined stressor effects
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33. What is a “risk-specific dose”?
A. A safe dose for children
B. A dose associated with a defined level of risk (e.g., 1 in 10,000)
C. A dose equal to the LOAEL
D. The average of NOAELs across species
Answer: B. NRC recommended expressing RfDs and similar values in probabilistic terms to aid comparison.
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34. Which EPA program was cited as a good example of considering human variability?
A. IRIS
B. Lead risk assessment
C. TRI
D. SNAP
Answer: B. EPA’s lead program explicitly considers children and population variability.
30
35. What term refers to real differences among individuals in susceptibility or exposure?
A. Uncertainty
B. Variability
C. Sensitivity index
D. Noise
Answer: B. Variability reflects actual differences, such as age, genetics, or lifestyle.
31
Toxicity Testing in the 21st Century (2007)
36. What challenge does in vitro testing face regarding metabolism?
A. Metabolism is not important
B. Human cell cultures may not replicate metabolism, leading to incomplete hazard detection
C. In vitro systems over-metabolize chemicals
D. All cells are metabolically equivalent
Answer: B. Without metabolic capability, in vitro tests may miss active metabolites.
32
37. Why might developmental toxicity require in vivo testing under the new paradigm?
A. In vitro tests cannot measure any toxicity
B. Developmental processes involve complex timing and tissue interactions not yet captured in vitro
C. Animals are cheaper
D. In vitro tests are too sensitive
Answer: B. Some effects, like neural migration, are difficult to model outside intact systems.
33
38. What is the role of toxicogenomics in the new testing strategy?
A. Replace all assays
B. Reveal pathway perturbations and help cluster chemicals by mechanism
C. Focus on liver damage only
D. Replace epidemiology
Answer: B. Gene expression profiling helps identify affected pathways and potential modes of action.
34
39. What does “Option III” in the NRC’s implementation strategy refer to?
A. Traditional testing
B. Tiered animal models
C. High-throughput in vitro testing + computational modeling + targeted in vivo testing
D. Full replacement of all animal tests
Answer: C. Option III is the realistic, phased approach endorsed by the committee.
35
40. What timeline did NRC expect for implementing the new testing paradigm?
A. Immediate (1–2 years)
B. 10–20+ years of gradual transition
C. 100 years
D. Never
Answer: B. Change will occur in stages as validation, infrastructure, and acceptance evolve.
36
41. What is IVIVE used for in the new paradigm?
A. Testing animals
B. Translating in vitro concentrations into human-equivalent doses
C. Extrapolating between species
D. Defining uncertainty
Answer: B. This bridges cell-level responses with real-world exposures.
37
42. What distinguishes high-throughput assays from traditional testing?
A. Focus on ecological endpoints
B. Automated, rapid, parallel testing of many chemicals at multiple concentrations
C. Use of highest doses only
D. Focus on food additives only
Answer: B. HTS enables screening of thousands of compounds quickly and efficiently.
38
43. What role do PBPK models play in the new strategy?
A. Create apical endpoints
B. Reduce in vitro sensitivity
C. Help estimate blood/tissue levels from external doses
D. Replace all regulatory values
Answer: C. PBPK models are essential for connecting lab results to population exposures.
39
44. What is a main ethical reason to reduce animal testing?
A. Animals are more variable
B. Animal labs are costly
C. Welfare concerns and impracticality of scaling to all chemicals
D. Public distrust of computers
Answer: C. The vision aligns with the 3Rs and recognizes the unsustainability of animal-heavy testing.
40
45. What is the purpose of targeted testing?
A. Repeating all assays
B. Fill in gaps not addressed by high-throughput or in vitro methods
C. Generate NOAELs
D. Increase throughput
Answer: B. Some endpoints, like developmental or metabolic effects, still require focused study.
41
Science and Decisions (2009)
51. What is “confirmation of utility” in NRC’s decision framework?
A. Checking math in the exposure calculation
B. Ensuring the risk assessment answers the decision question and is actionable
C. Comparing RfDs to cancer slope factors
D. Confirming the budget was not exceeded
Answer: B. This stage helps determine if the assessment is informative for choosing among management options.
42
52. Which of the following is an “implicit default” identified by NRC?
A. 10-fold intraspecies UF
B. Excluding data-poor chemicals from analysis, implying zero risk
C. Using RfCs for inhalation
D. Linear cancer modeling
Answer: B. NRC noted that ignoring a chemical due to lack of data may implicitly assume it poses no risk—an unstated default.
43
53. What example did NRC give of EPA successfully incorporating variability?
A. Trichloroethylene (TCE)
B. Benzene
C. Carbon monoxide
D. Arsenic
Answer: A. EPA’s TCE assessment included TK and TD variability in humans.
44
54. What is “problem formulation” intended to do?
A. Prioritize only cancer endpoints
B. Define the assessment scope, management options, and decision context early
C. Avoid data gaps
D. Select default UFs
Answer: B. Clear problem formulation aligns the assessment with decisions it must inform.
45
55. What did NRC suggest for low-dose cancer risk when MOA is unknown?
A. Threshold model
B. Default to linear extrapolation
C. Only in vitro testing
D. Assign a hazard quotient
Answer: B. Unless a nonlinear MOA is demonstrated, EPA assumes risk is proportional to dose at low levels.
46
56. What did NRC say about integrating risk assessment and management?
A. Keep them separate
B. Embed risk assessment within decision-making framework to compare options
C. Delay management until data perfection
D. Use stakeholder vote to pick risk model
Answer: B. The Silver Book ties assessment and management more closely than the Red Book did.
47
57. How can default uncertainty factors be improved?
A. By removing them
B. Using data-derived extrapolation factors (DDEFs) when chemical-specific info is available
C. Increasing all to 100
D. Basing on survey data
Answer: B. NRC supports replacing defaults with data when scientifically justified.
48
58. What aspect of communication did NRC emphasize for uncertainty?
A. Omit it for clarity
B. Use ranges without explanations
C. Explicitly communicate variability and uncertainty to users and stakeholders
D. Only share after decisions are made
Answer: C. Transparent communication builds understanding and credibility.
49
59. What change did NRC propose for setting RfDs?
A. Eliminate them
B. Fix at lowest tested dose
C. Express as risk-specific doses (e.g., corresponding to 1-in-100,000 risk)
D. Double all for safety
Answer: C. Risk-specific RfDs support better comparisons across health endpoints.
50
60. How does EPA typically treat non-cancer endpoints?
A. With no thresholds
B. As having a threshold below which no effects occur
C. As more important than cancer
D. Only qualitatively
Answer: B. RfDs assume thresholds exist for non-cancer outcomes—though NRC notes this may oversimplify reality.
51
Toxicity Testing in the 21st Century (2007)
61. What is Option III in NRC’s toxicity testing strategy?
A. Keep using rodent bioassays
B. Random testing by need
C. A blend of high-throughput in vitro testing, computational models, and targeted in vivo testing
D. Full automation of animal studies
Answer: C. Option III was the NRC’s preferred transition strategy for the next 10–20 years.
52
62. What is “systems biology” used for in this paradigm?
A. Model how biological networks respond to chemical perturbations
B. Estimate lab costs
C. Eliminate animal testing
D. Score test precision
Answer: A. These models help interpret how in vitro effects scale to tissue-level or organism-level outcomes.
53
63. What advantage do human in vitro assays offer over animal tests?
A. They’re less accurate
B. They better reflect human biology and reduce interspecies uncertainty
C. They test behavior
D. They generate apical endpoints directly
Answer: B. Testing in human cells improves relevance compared to extrapolating from rodents.
54
64. What is the role of ToxCast in implementing NRC’s vision?
A. High-throughput in vitro testing of environmental chemicals to generate biological profiles
B. Genetically modify mice
C. Control field exposures
D. Standardize peer review
Answer: A. ToxCast uses cell- and pathway-based assays to inform prioritization and hazard evaluation.
55
65. Why is “targeted testing” still needed?
A. To address complex endpoints and fill gaps that HTS can’t cover, such as metabolism or developmental effects
B. To test drugs
C. To generate NOAELs
D. To meet regulatory quotas
Answer: A. Not all effects are detectable in in vitro platforms—some require in vivo investigation.
56
66. How might IVIVE inform regulatory decisions?
A. By making rules
B. By predicting human exposure doses corresponding to in vitro effect levels
C. By comparing UFs
D. By calculating LD50
Answer: B. IVIVE uses PK modeling to relate cellular concentrations to real-world exposures.
57
67. What role does toxicogenomics play in new toxicity testing?
A. Focus on enzymes
B. Reveal gene-level effects and identify disrupted pathways
C. Replace all tests
D. Rank chemical volatility
Answer: B. Genomic profiling can show broad responses to chemicals and help cluster chemicals by MOA.
58
68. What limitation exists in current in vitro testing regarding metabolism?
A. None
B. Many cell systems lack metabolic competence, possibly missing toxic metabolites
C. Cells over-metabolize
D. Only phase I is assessed
Answer: B. Lack of full metabolic pathways means some in vitro systems may fail to activate pro-toxins.
59
69. Why are in vitro assays particularly helpful for low-dose effects?
A. They ignore thresholds
B. They can test over many concentrations, including environmentally relevant levels
C. They replicate tumors
D. They only test LD50
Answer: B. This enables observation of subtle pathway perturbations not detectable in high-dose-only animal studies.
60
70. How are chemicals prioritized for further evaluation in the new paradigm?
A. Alphabetically
B. Based on HTS results showing pathway perturbation or bioactivity profiles
C. Random lottery
D. Cost
Answer: B. Activity in key assays signals a need for follow-up and potential concern.
61
Science and Decisions (2009)
76. Why did NRC propose shifting from a binary “safe/unsafe” framework to a quantitative risk model for non-cancer effects?
A. Because RfDs are no longer legal
B. To allow better comparison across effects and levels of concern, even at low doses
C. To favor cancer over non-cancer endpoints
D. To eliminate uncertainty factors
Answer: B. Quantifying risk below traditional thresholds enables more transparent and flexible decision-making.
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77. Which factor does NRC say can shift the population dose–response curve for non-cancer effects?
A. Random error
B. Background exposure and pre-existing disease
C. Cost of chemical regulation
D. In vitro artifact
Answer: B. Background factors can increase susceptibility and result in low-dose responses in some individuals.
63
78. What is the practical implication of redefining RfD as a “dose with X% risk”?
A. Risk managers can choose different RfDs depending on acceptable risk levels
B. RfD will replace slope factors
C. All risks become equal
D. Cancer is ignored
Answer: A. This approach enables explicit tradeoff analysis and transparency about what a given dose implies.
64
79. What type of uncertainty is potentially reducible with research?
A. Model uncertainty
B. Variability
C. Genetic heterogeneity
D. Dietary intake differences
Answer: A. Uncertainty stems from lack of knowledge and can be reduced, unlike inherent variability.
65
80. What does the NRC say about communicating distributions of risk rather than point estimates?
A. It confuses stakeholders
B. It better reflects the reality of human variability and increases decision transparency
C. It’s less conservative
D. It hides uncertainty
Answer: B. Presenting full distributions (e.g., 5th to 95th percentile) shows how risk varies across a population.
66
81. Which is a core component of adaptive management in environmental health?
A. Fixed standards
B. Continuous learning and adjustment based on monitoring outcomes
C. Zero uncertainty tolerance
D. Permanent bans after first finding
Answer: B. Adaptive management treats implementation as an experiment, refining based on feedback.
67
82. What is a benefit of early stakeholder engagement?
A. Helps identify key issues, builds trust, and makes assessments more relevant
B. Delays the process
C. Decreases scientific accuracy
D. Replaces data collection
Answer: A. Engaging stakeholders improves problem formulation and the usefulness of assessments.
68
83. Which of the following would most likely be excluded from a cumulative risk assessment, according to NRC critique?
A. Pesticide mixtures
B. Psychosocial stressors
C. Industrial solvents
D. Air pollutants
Answer: B. Non-chemical stressors are often ignored, though NRC says they should be included.
69
84. Which recommendation did NRC make regarding use of “defaults”?
A. Replace all defaults immediately
B. Keep defaults but establish clear criteria for when data can override them
C. Eliminate peer review
D. Use defaults only in cancer assessments
Answer: B. Defaults are necessary, but their use should be transparent and data-responsive.
70
85. Which is an example of “risk-risk” tradeoff analysis?
A. Comparing two exposure durations
B. Banning a solvent that increases indoor air pollution due to less effective replacements
C. Setting the same standard for all chemicals
D. Estimating margins of exposure
Answer: B. A decision to reduce one risk (solvent toxicity) could increase another (ventilation-based exposures).
71
Toxicity Testing in the 21st Century (2007)
86. What key capability makes high-throughput assays useful for modern risk assessment?
A. Manual dosing
B. Parallel, automated testing of many chemicals and concentrations
C. Avoiding detection of low-dose effects
D. Cloning animals
Answer: B. HTS allows broad, efficient screening of thousands of compounds.
72
87. Why is it important to test across a range of concentrations, not just high doses?
A. High doses are illegal
B. Low-dose effects may occur in real-world exposures and should be detected
C. It eliminates the need for modeling
D. Cell assays can’t handle high doses
Answer: B. Many relevant biological effects happen at low exposure levels, especially in humans.
73
88. What challenge exists in extrapolating from in vitro data to human risk?
A. Lack of interest
B. Translating in vitro concentrations to actual human exposures via pharmacokinetics
C. Assays are never reproducible
D. In vitro cells never respond
Answer: B. In vitro to in vivo extrapolation (IVIVE) is necessary to interpret relevance.
74
89. What endpoint is not well-covered by current in vitro assays?
A. Enzyme inhibition
B. Cytotoxicity
C. Developmental neurotoxicity
D. Receptor activation
Answer: C. Complex developmental processes still require in vivo evaluation in many cases.
75
90. What’s the long-term vision for Option IV in NRC’s strategy?
A. Add more rats
B. Fully in vitro, computational testing with no animal use
C. No testing
D. Field-based randomized trials
Answer: B. Option IV is the ultimate animal-free testing model.
76
91. Why are animal studies still included in Option III?
A. Because computers are unreliable
B. To resolve issues like metabolism, systemic responses, and life-stage effects not yet captured in vitro
C. Regulatory inertia
D. Public demand
Answer: B. Targeted animal testing fills critical gaps during the transition.
77
92. What advantage does ToxCast offer regulators?
A. Traditional data only
B. Mechanistic data on many chemicals for prioritization and grouping
C. Random test ordering
D. Manual analysis
Answer: B. ToxCast helps group chemicals by bioactivity and determine which to investigate further
78
93. What does a “toxicity pathway” refer to in the NRC paradigm?
A. Metabolic elimination
B. Cellular network that, when perturbed, leads to adverse effects
C. Transport mechanism in tissues
D. Dose calculation
Answer: B. These pathways are central to modern toxicology’s mechanistic focus.
79
94. What type of modeling supports dose–response estimation in the new approach?
A. Behavioral analysis
B. Systems biology modeling
C. Risk matrices
D. QSAR only
Answer: B. Systems models help relate pathway-level changes to population outcomes.
80
95. Why did NRC stress validation of new methods?
A. To meet animal welfare standards
B. To slow implementation
C. To ensure in vitro tests are reliable, reproducible, and accepted for regulatory use
D. To delay regulations
Answer: C. Validation builds scientific and regulatory confidence in new tools.
81
96. What is the main ethical framework underlying animal-use reduction?
A. QALY
B. The 3Rs – Replace, Reduce, Refine
C. Lethality first
D. Maximize cost
Answer: B. The 3Rs are a long-standing principle guiding ethical animal research.
82
97. What gap does current toxicology face regarding chemical universe coverage?
A. Only 10 chemicals exist
B. Tens of thousands of chemicals lack adequate hazard data
C. Too many models
D. All chemicals are tested already
Answer: B. The existing backlog is a major driver of HTS development.
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98. What human variability factor can now be explored in vitro?
A. None
B. Genetic diversity using cell lines from diverse donors
C. Liver weight
D. Food intake
Answer: B. Diverse human cells can help estimate population-level response distributions.
84
99. What is the “long-term goal” of the NRC vision?
A. Status quo
B. High-throughput, animal-free, human-relevant testing framework
C. Cross-species testing
D. Field experiments only
Answer: B. This modern system is data-rich, fast, and focused on human biology.
85
100. What is the final recommendation NRC gave about implementation?
A. Keep changes quiet
B. Wait until all assays are complete
C. Launch a coordinated, phased approach with committed funding, oversight, and independent review
D. Outsource all testing immediately
Answer: C. Strategic implementation and periodic evaluation are essential for success.
