Series 5: TOXICOLOGY Question and Answer bank -Risk Assessment
Cont’d from series 4
Q. Define risk
Risk is
defined as the probability of an adverse outcome based upon the exposure and
potency of the hazardous agent(s).
Q. Define safety
Means practical
certainty that injury will not result from use of a substance under specified
condition of quantity and manner of use.
Q. Define benefit-to-risk-ratio
This implies that
even a toxic agent may warrant use if its benefits for a significant number of
people are much greater than the dangers,
Q. Describe briefly risk assessment
Risk assessment
is a quantitative assessment of the probability of deleterious effects under
given exposure conditions. It
requires an integration of both qualitative as well as quantitative scientific
information. For example, qualitative information about the overall evidence
and nature of the endpoints, and hazards are integrated with quantitative
assessment of the exposures, host susceptibility factors, and the magnitude of
the hazard. A description of the uncertainties and variability in the estimates
is a significant part of risk characterization and an essential component of
risk assessment.
Q. Define hazard
It
is the qualitative description of the adverse effect arising from a particular
chemical or physical agent with no regard to dose or exposure. The term hazard
is related to the risk, but it mainly expresses likelihood or probability of
danger, irrespective of dose or exposure.
Or
A property or set of properties of the chemical substance that may
cause an adverse health or ecological effect provided if there is an exposure
at a sufficient level.
Q. Define acceptable risk
It is the probability
of suffering a disease or injury during exposure to a substance, which is
considered to be small but acceptable to the individual.
Q. Define acceptable exposure
It is the
unintentional contact with a chemical or physical agent that results in the
harmful effect.
Q. Define margin of
exposure (MOE)
Margin of exposure is defined as the ratio
of the no-observed adverse-effect-level (NOAEL) for the critical effect to the
theoretical, predicted, or estimated exposure dose or concentration.
Q. Define threshold limit values (TLV)
The TLV refers to the airborne concentration
of a substance to which it is believed a worker can be exposed
day after day for a working lifetime without adverse effects.
These values are expressed as time weight concentration for 7 to 8 hr work day
and for 40 week.
Q. Define No Observed Effect Level / Concentration
(NOEL/ NOEC)
NOEL/ NOEC is the highest dose
level/concentration of a substance that under defined conditions of exposure
causes no effect (alteration) on morphology, functional capacity, growth,
development or life span of the test animals.
Q. Define No Observed Adverse Effect Level /
Concentration (NOAEL / NOAEC).
NOAEL/ NOAEC is the
highest dose level/concentration of a substance that under defined conditions
of exposure causes no observable/detectable adverse effect (alteration) on morphology,
functional capacity, growth, development or life span of the test animals.
NOAEL / NOAEC is a variant of NOEL/ NOEC that specifies only that the effect in
question is adverse.
Q. Define Lowest Observed Adverse Effect Level /
Concentration (LOAEL/ LOAEC)
LOAEL / LOAEC is the highest exposure
level/dose level/concentration of a substance under defined conditions of
exposure an observable/detectable effect (alteration) on morphology, functional
capacity, growth, development or life span of the test animals is observed.
Q. Define
Reference Dose/Concentration (RfD/RfC): For
non-cancerous effects oral intake (RfD) or an inhalation reference
concentration (RfC) for airborne materials is calculated using the NOAEL or
LOAEL as a starting point. These values are developed from experimentally
determined NOAEL or LOAEL.
Preliminary evaluation of risk assessment.
Q.
Describe briefly requirement of data for preliminary evaluation of risk
assessment in human health?
The
type of data required for preliminary evaluation is summarized in THE FOLLOWING Table
Table: Data required for preliminary evaluation of risk assessment in human
health
Data required
|
Quality data
|
Physiochemical processes
|
Observed effects on humans
|
Toxicity
|
Derived from animal studies
|
Release /transport / uptake
|
Applicable to expected dosage
|
Chemical physical interaction
|
Most current to support specific conclusions
|
Basic elements of risk assessment
Q. What are the basic elements involved in the process of
risk assessment?
Four steps used in risk analysis
include:
a)
Hazard identification
b)
Dose response evaluation
c)
Exposure assessment
d)
Risk characterization.
Explanation:
The initial step is hazard identification, which identifies the chemical that
present a risk to human health. This is a qualitative step, which involves a
thorough evaluation of current scientific evidence, including animal studies,
human studies, epidemiological studies and cellular studies. If a chemical is
identified as a potential hazard to human health, the process continues.
The second
step of risk analysis, is the dose-response evaluation, which is a quantitative
step. This step measures the magnitude of the response at different doses. If
available, human studies showing the potency of the agent, or its ability to
produce negative health effects in humans, are also assessed.
The next
step, is the exposure assessment. This step seeks to estimate people's level of
exposure. Exposure refers to the amount of a substance in the environment, and
such an estimation include the length of exposure, duration of exposure and
route of exposure, among other considerations. The difference between the
actual dose, or level of a substance taken in, and the amount of the substance
measured (exposure) is included in this assessment. This assessment must also
quantify various properties of a substance-e.g. volatility, as well as the
group exposed and whether the exposure is continuous, intermittent, short term,
long term or chronic.
The final
step is risk characterization. This step uses all of the previously gathered
information through the first three steps, and creates a picture of risk that
describes its likelihood, severity and consequences. This characterization
includes an estimate of the negative effects-e.g. deaths or cancer cases per
100,000 people. The final step also takes into account any limitations and or
uncertainties that were involved in creating the estimate.
Hazard identification
Q. Name
four steps involved in hazard identification used for risk assessment process.
Hazard
identification involves the following four steps
(a) Epidemiology
(b) Animal
studies
(c) Short
term assays
(d) Structure
activity relationship
Dose response assessment
Q. Name
three steps involved in dose response assessment used for risk assessment
process.
Dose
response assessment involves the following three steps
(a) Quantitative
toxicity information collected
(b) Dose-response
relationship established
(c) Extrapolation
of animal data to human
Exposure assessment
Q. Name
three steps involved in exposure assessment used for risk assessment process.
Exposure
assessment involves the following three steps
(a) identification
of exposed populations
(b) identification
of routes of exposure
(c) identification
of degree of exposure
Risk characterization
Q. Name
three steps involved in risk characterization used for risk assessment process
Risk
characterization involves the following three steps
(a) Estimation
of the potential for adverse health effects to occur
(b) Evaluation
of uncertainty
(c) Risk
information summarized
Q. Discuss at least three limitations inherent in risk
analysis.
Limitations
to risk analysis include:
(a)
Uncertainty of effect
(b) Variability
of exposure
(c) Possibility of multiple exposures
Explanation:
Often, too little is known about any substance to provide any real assurance.
Despite laboratory testing and careful risk analysis, uncertainty will remain.
Interpersonal variability may also strongly affect a specific individual's
risks, as a general overview may not identify people who may be more sensitive
to exposures than others, and thus may have a higher "safe" dose.
Multiple-exposures are difficult to study, although they certainly exist in the
real world. In addition, any additive effects are ignored, which may heighten
the risk and which are sure to occur outside of the laboratory. However,
despite its limitations, risk analysis is still an important tool to explore
and understand risks in the modern world.
Establishment of an acceptable reference dose (RfD)
Q.
How an acceptable
reference dose (RfD) is established for risk assessment?
Acceptable
reference dose (RfD) is established by the following relationship.
RfD= NOAEL/(UF ×MF)
ADI = NOAEL/(UF ×MF)
Where
the uncertainty factor (UF) is typically equal to 100 and modifying factor (MF).
For cancer end points, the only strictly
safe exposure level is at zero dose, although for very small doses the risk is
extremely low and is not considered significant.
Explanation:
Approaches for
characterizing dose-response relationships include identification of effect
levels such as LD50 (dose producing 50 % lethality),
LC50 (concentration producing
50 % lethality), ED10 (dose producing 10% response), as well as
NOAELs. NOAELs have traditionally served as the basis for risk assessment
calculations, such as reference doses or acceptable daily intake (ADI) values. Reference doses (RfDs) or concentrations (RfCs) are estimates of a daily exposure
to an agent that is assumed to be without adverse health impact in humans. The
ADIs are used by WHO for pesticides and food additives to define “the daily
intake of chemical, which during an entire lifetime appears to be without
appreciable risk on the basis of all known facts at that time”. Reference doses
and ADI values typically are calculated from NOAEL values by dividing
uncertainty (UF) and / or modifying factors (MF). Tolerable daily intakes (TDI) can be used to describe intakes for chemicals
that are not “acceptable” but are “tolerable” as they are below levels thought
to cause adverse health effects. These are calculated in a manner similar to
ADI. In principle, dividing by the uncertainty factors allows for interspecies (animal-to-human) and intra species (human-to-human) variability with default
values of 10 each. An additional uncertainty factor is used to account for
experimental inadequacies—for example, to extrapolate from short exposure -
duration studies to a situation more relevant for chronic study or to account
for inadequate numbers of animals or other experimental limitations. If only a
LOAEL value is available, then an additional 10-fold factor commonly is used to
arrive at a value more comparable to a NOAEL. Traditionally, a safety factor of 100 is used for RfD calculations to extrapolate
from a well-conducted animal bioassay (10-fold factor animal to human) and to
account for human variability in response (10-fold factor human-to-human
variability).
Assumption
is made that exposure below a certain level, the NOAEL, will have no adverse
health consequences. An acceptable reference dose, RfD, is then established.
To be cont’d
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