Ch 3- Risk Assessment-HI and DE Assessment

Question 1

Forerunners prior to FORMAL risk assessment

Answer 1

1) 1970s plan of Congress to protect human and environmental health
2) ACGIH -TLVs
3) FDAs- ADI/ TDI, Delaney Clause

Question 2

Where is risk assessment defined?

Answer 2

In 1983

In the Red Book “ Risk Assessment in the Federal Government: Managing the Process (Red Book)

Four Basic framework steps (HI, DE assessment, Exposure Assessment, Risk charac)

Question 3

Whats did the National Academy of Sciences (NAS) 1994 report
entitled ‘Science and Judgment in Risk Assessment’ emphasize?

Answer 3

1. Use a combination of combination of qualitative and quantitative approaches
2. How to deal with uncertainities and data gaps

Question 4

What was the answer to deal with challenges in RA ?

Answer 4

Congressional Commission on Risk Assessment and Risk Management (Risk Commission, 1997)

SUGGESTED:

1. the framework for RISK MANAGEMENT (6 steps)
2. engage stakeholders
3. do away with single-chemical, single- exposureapproach

Question 5

Whats is a major challenge for A major challenge for risk assessment, risk communication, and risk management?

Answer 5

Show biological plausibility and clinical significance of concludions from Epi studies

Use:

• Biomarkers of exposure
• Biomarkers of effect
• Differences in indi susceptability

Question 6

How is toxicity of closely related chemicals in mixtures evaluated (eg: TCDD with other related chlorinated and brominated dioxins, dibenzofurans etc) ?

Answer 6

using toxicity equivalence factors (TEFs)

Question 7

what is a formula to calculate toxicity in mixutres?

Answer 7

[conc. of chemcial 1 * TEF] +

[conc. of chemical 2 *TEF] +

[conc. of chemical 3 *TEF]

.

.

.

etc.

Question 8

Where has there been renewed interest to use SARs to predict toxcity?

Answer 8

nanomaterials (due st the size of the # of cmpds.)

Question 9

What info can short term assays and in vitro assays provide to risk assessment?

Answer 9

MOA

Question 10

Whats is the advantage of lifetime todent bioassays for HI?

Answer 10

1. Provide additional mechanistic data
2. look for non-cancer enpoints

(integrate it with data from short term assays, epi studies)

Question 11

The cancer bioassay, originally designed for hazard identification, is frequently used to evaluate dose–response. But what are the shortcomings?

Answer 11

• Use of few animals
• USe of very high odses ( for extrapolation of low-dose response)
• high doses may saturate important metabolism and elimination pathways

This has LIMITED the use of cancer bioassays for human cancer risk prediction

Question 12

Whats are +ve indicators of carcinogenicity of a chemical in rodent carcinogenicity assays?

Answer 12

Increase in tumor multiplicity

induction of rare tumors

shorter latency period

Question 13

reactions between nucleophilic toxicants and electrophiles is rare but DOES occur in whihc case?

Answer 13

Reaction of _amines and hydrazides_ with the
_aldehyde pyridoxal_ (a cosubstrate for several enzymes)