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
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Quality data
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Physiochemical processes
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Observed effects on humans
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Toxicity
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Derived from animal studies
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Release /transport / uptake
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Applicable to expected dosage
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Chemical physical interaction
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Most current to support specific conclusions
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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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