chapter 16 - risk assessment

indicate which of the following are true:

a) acute toxicity studies are primarily for the determination of. mutagenicity

b) sub-chromic toxicity tests are used for the measurement of dose responses

c) eco toxicity studies utilize tests in Daphnia

d) teratogenicity tests are party of reproductive toxicity studies

which of the following are important in risk assessment?

a) exposure level or dose

b) hazard

c) NOEL

d) benefit

e) ADI

f) cost

g) TLV

define and describe the following acronyms: NOAEL, ADI, TLV

NOAEL: no observed adverse effect level

• is the dose or exposure level of a chemical which has no demonstrable adverse effect on a biological system. the value may be derived from the dose-response relationship.

ADI: acceptable daily intake

• is usually applied to food additives or contaminants such as pesticides. it is the calculated amount of a substance to which humans are permitted to be exposed safely. it is calculated from the NOAEL

TLV: threshold limit value

• is the upper permissive limits of airborne concentrations of substances

define and describe RA. give examples to support your answer

risk assessment (RA) is a mathematical concept that refers to the likelihood of undesirable effects resulting from exposure to a chemical. examples include the incorporation of therapeutic drugs in the biomedical community, release of chemicals for environmental health, such as pesticides, and potentially hazardous substances such as food additives

risk

the probability that an toward or unpredictable event will result in an adverse effect under specific exposure conditions

Risk = hazard * exposure

hazard

the capacity of a substance to cause an adverse effect

maximum tolerated dose (MTD)

dose of a substance which causes not more than a 10% weight decrease and does not cause death or any clinical signs of toxicity which would shorten the life span of an animal exposed for 90 days

what are the objectives of performing RA?

1. determine if the chemical has the potential to be a hazard to humans in the environment

2. likelihood of persistence of the chemical in the environment and if bioaccumulation increases its hazard potential

3. probability that sensitive human and ecological populations exposed to significant levels of the chemical are hazardous

4. indication of hazard risk to human health

5. if the likelihood of exposure via use or production poses an unhealthy situation

who said that the dose makes the poison?

Paracelsus

risk management

consideres alternative policies for the most appropriate course of regulatory action based on the results of RA and social economic, and political considerations

quantitative RA

an estimation of toxic exposure concentrations or doses that, within a defined probability level, lead to specific increases in lifetime incidence rates for an undesirable consequence associated with the toxic substance

what are the four steps of the quantitative RA evaluation process?

1. hazard identification

2. dose-response assessment

3. exposure assessment

4. risk characterization

hazard identification

evaluation of the toxic effects of the chemical

dose-response assessment

quantifies identifiable hazards an evaluates the relationship between dose and adverse effects in humans; quantitation of existing hazards; extrapolation between experimental doses from in vivo to realistic exposures

exposure assessment

an estimation of the intensity, frequency, and duration of exposure for humans to the hazardous substance

exposure converts a chemical from a hazard to a risk

risk characterization

estimation of the incidence of adverse effects under the various conditions of human exposure

an integration of risk assessment and exposure assessment - the probability of the occurrence of the adverse effect on humans exposed to the chemical

one-hit model

assumes that cancer involves only one stage and a single molecular event is sufficient to induce a cellular transformation; ultra conservative - single exposure causes cancer

linearized multistage model (EPA)

determines the cancer slope factor calculated to predict cancer risk at a specific dose; assumes a linear extrapolation to zero dose threshold, i.e. an estimate of the probability that n individual will develop cancer if exposed to the chemical for 70 years

cancer slope factor that can be used

]slope = q1* used to predict cancer at a specific dose

multi-hit model

assumes several interactions are needed before a cell can be transformed. least conservative

probit model

assumes log normal distribution for tolerances of exposed population. is sometimes used but generally considered inappropriate for assessing cancer risk

physiologically based pharmacokinetic (PBPK)

incorporate pharmacokinetic and mechanistic data into the extrapolation process. requires extensive data and is becoming commonly used

threshold

defines acceptable exposure levels within human populations; represent a range of the lowest possible exposures that are tolerated by humans in the environment or in an occupational setting without risk of adverse health effect

what is the 2 step process in which the IARC database applies to RA of carcinogens?

1. qualitative assessment of data from hazard identification

2. quantitation of risk for definitive or probable human carcinogens

describe the gross of IARC carcinogenicity classification

Group 1: agent is carcinogenic to humans

Group 2A: agent is probably carcinogenic in humans

Group 2B: agent is possibly carcinogenic in humans

Group 3: agent is not classifiable as to its carcinogenicity

Group 4: agent is probably not carcinogenic in humans

what are the limitations of in vivo studies?

the requirement to see an increase in tumors, doses close to the MTD are used, and the precision of the mathematical model is largely irrelevant if the quality of the original toxicological data is poor

hydrazine

a weak carcinogen at high doses; causes DNA methylation at high doses; equivalent doses cause severe hepatoxic damage; acute toxicity is responsible for the observed carcinogenicity

Delaney Clause

prohibited all compounds that show carcinogenicity; was repealed in 1996

how are biomarkers used in risk assessment?

calculate internal dose of compound; develop NOAEL and dose response relationship; determine sensitive population groups; laboratory testing to realistic standards; epidemiologya

true or false: risk assessment is very precise and is based solely on science

false

risk assessment is imprecise and is not based solely on science