Risk assessment exposed populations

Risk assessment pertains to characterization of the probability of adverse health effects occurring as a result of human exposure. Recent trends in risk assessment have encouraged the use of realistic exposure scenarios, the totality of available data, and the uncertainty in the data, as well as their quality, in arriving at a best estimate of the risk to exposed populations. The use of "worst case" and even other single point values is an extremely conservative approach and does not offer realistic characterization of risk. Even the use of arithmetic mean values obtained under maximum use conditions may be considered to be conservative and not descriptive of the range of exposures experienced by workers. Use of the entirety of data is more scientific and statistically defensible and would provide a distribution of plausible values. 

Risk characterization is the most important and final part of a risk assessment. It summarizes and interprets the information from hazard identification, dose-response, and exposure steps, identifies the limitations and uncertainties in risk estimates, and communicates the actual likelihood of risk to exposed populations. The uncertainties identified in each step in the risk assessment process are analyzed and the overall impact on the risk estimate(s) is evaluated quantitatively and/or qualitatively. 

The antithesis of formulaic human health risk assessments for populations exposed to environmental contaminants, i.e., a post hoc process, is the precautionary principle, an ante hoc rationale. This approach appears to some as relatively draconian in its prescriptive formulation, i.e., no substances should be released into the human environment unless the likelihood of harm to health is determined to be acceptably small. 

A risk estimate indicates Uie likelihood of occurrence of the different types of health or enviroinnental effects in exposed populations. Risk assessment should include both liuimn health and environmental evaluations (i.c., impacts on ecosystems). Ecological impacts include actual or potential effects on plants and animals (other than domesticated species). The number produced from the risk characleriznlion, representing the probability of adi crse... 

Some animal studies indicate that dietary exposure to methyl parathion causes decreased humoral and cellular responses (Shtenberg and Dzhunusova 1968 Street and Sharma 1975). A more recent, well-designed animal study that included a battery of immuno/lymphoreticular end points showed few effects at the nonneurotoxic doses tested (Crittenden et al. 1998). No adequate studies are available in humans to assess the immunotoxic potential of methyl parathion. Therefore, studies measuring specific immunologic parameters in occupationally exposed populations are needed to provide useful information. Further studies are also needed to investigate the mechanism for methyl parathion-induced immunotoxicity since this information would help to identify special populations at risk for such effects. 

Assessments of risks associated with the use of chlorpyrifos insecticide products for workers have been made. The assessments are based on the results of field studies conducted in citrus groves, a Christmas tree farm, cauliflower and tomato fields, and greenhouses that utilized both passive dosimetry and biomonitoring techniques to determine exposure. The biomonitoring results likely provide the best estimate of absorbed dose of chlorpyrifos, and these have been compared to the acute and chronic no observed effect levels (NOELs) for chlorpyrifos. Standard margin-of-exposure (MOE) calculations using the geometric mean of the data are performed however, probability (Student s f-test) and distributional (Monte Carlo simulation) analyses are deemed to provide more realistic evaluations of exposure and risk to the exposed population. 

The output of an exposure and risk assessment will usually describe the levels of exposure and quantity the population exposed for both humans and other biota, and will estimate the associated probabilities of the incidence of adverse health effects. Population exposure or risk, obtained by multiplying the individual (per capita) exposure or risk by the numbers exposed at each level of exposure, may also be a useful measure of impact. Various analyses can be performed on the results, for example, comparison of exposures in a particular geographic area against national average exposure levels. Likewise, for the same pollutant, environmental risks due to a particular industry might be compared against risks associated with occupational or household activities. In addition, the health risk of different substances could be compared for priority setting. 

The following example is based on a risk assessment of di(2-ethylhexyl) phthalate (DEHP) performed by Arthur D. Little. The experimental dose-response data upon which the extrapolation is based are presented in Table II. DEHP was shown to produce a statistically significant increase in hepatocellular carcinoma when added to the diet of laboratory mice (14). Equivalent human doses were calculated using the methods described earlier, and the response was then extrapolated downward using each of the three models selected. The results of this extrapolation are shown in Table III for a range of human exposure levels from ten micrograms to one hundred milligrams per day. The risk is expressed as the number of excess lifetime cancers expected per million exposed population. 

Due to this, it is necessary to assess the risk to human health and the environment due to the exposure to these chemical additives. In this chapter the impacts that a substance can cause to a certain receptor (humans and the environment) and the harms to the receptor at different exposure levels are identified in hazard identification and hazard characterization steps, respectively. Exposure assessment takes into account the amount, frequency, and duration of the exposure to the substance. Finally, risk characterization evaluates the increased risk caused by such exposure to the exposed population. 

Exposure assessment is one of the most important steps in risk assessment. It is the process that predicts or estimates the amount of the substance under study that reaches the human body. To assess the exposure, it is necessary to define in detail the exposure pathway, the route of exposure, the concentration of the pollutant in the particular media, the contact rate, the frequency of exposure, and the population exposed (age, gender, and vulnerable population, among others). A general equation (Eq. 1) to determine the exposure dose is as follows ... 

The last step in risk assessment is the risk characterization where the probability and the severity of adverse health effects in the exposed population are assessed. 

In order to understand the use and intent of the various immunotoxicology regulatory guidelines and guidance documents, the difference between two concepts familiar to toxicologists should be emphasized. Hazard, identification refers to a method which is essentially qualitative that is, it is designed to detect the ability of a test article to produce a certain (in the context of toxicology) adverse effect, without reference to exposure issues. Risk assessment, on the other hand, takes into consideration method, dose, and duration of exposure, condition(s) of the exposed population, and concurrent... 

Note that in these several examples certain kinds of assumption are used to estimate intakes. In the TCE examples all adults were assumed to consume 2 liters of water each day and were also assumed to weigh 80 kg. Obviously in any population exposed to the contaminated water, it is unlikely that these two assumptions apply with high accuracy to any actual individuals. In fact the assumptions may be quite inaccurate for some individuals, even while they might be reasonably representative, on average, for most. It is in fact not possible to conduct risk assessments without the use of assumptions such as these, and so the individuals that are the subjects of typical risk assessments might be described as generic rather than actual. As will become clear in the later chapters on risk assessment, this type of generic evaluation is appropriate and useful for the purposes of public health protection. 

Defining the risk assessment problem to be evaluated should precede entering the four-step process set out in Figure 7.1, Chapter 7. This means identifying the population that is to be the subject of the assessment, and specifying the conditions under which it is or may come to be exposed to a chemical or mixture of chemicals. Formulations of the problem might be similar to any of the five examples offered at the beginning of Chapter 7. 

For the purposes of risk assessment the exposed individuals are, in a way, hypothetical, not actual people. By this is meant that they will be assumed to exhibit certain characteristics that make it possible to reach general conclusions regarding the magnitude and duration of their exposure to the chemical of interest, and also their relative sensitivity to its toxic effects. It may be that there are actual people in the population having characteristics closely resembling those assumed by the risk assessor, but it is not possible to know (except in highly unusual circumstances) who those people are. ... 

Some risk assessors describe the process of setting up for risk assessment as developing a scenario. A scenario is a description of the population that is of interest and the way such a population is or could become exposed to a chemical or group of chemicals. Some typical scenarios for risk assessment are set out in Table 8.1, in abbreviated form. 

Exposures in the population of interest will generally reveal that incurred dose is only a small fraction, and sometimes a very tiny fraction, of that at which toxic responses has been or can be directly measured, in either epidemiology or animal studies. Occupational populations (Table 8.1, Scenario C) may be exposed at doses close to those for which data are available, but general population exposures are usually much smaller. Thus, to estimate risk it will be necessary to incorporate some form of extrapolation from the available dose-response data to estimate toxic response (risk) in the range of doses expected to be incurred by the population that is the subject of the risk assessment. 

In some cases the available dose-response data will have originated from studies by one route of exposure (say, inhalation), but the population of interest is or might be exposed by other routes, say the oral one. Completion of a risk assessment prior to the development of new oral data will require a biologically justifiable method for extrapolating results from one route of exposure to another. 

Hazard assessment is A process designed to determine the possible adverse effects of an agent or simation to which an organism, system or (sub) population could be exposed. The process includes hazard identification and hazard characterization. The process focuses on the hazard in contrast to risk assessment where exposure assessment is a distinct additional step. ... 

If actual or potential exposure has been identified, a quantitative exposure assessment is necessary. Exposure levels/concentrations for each potentially exposed population need to be derived from the available measured data and/or from modeling. A range of exposure values to characterize different subpopulations and scenarios may result. These results are taken forward to the risk characterization where they are combined with the results of the effects assessment in order to decide whether or not there is concern for the human population exposed to the substance. In some cases all three types of exposure estimates may contribute to an overall exposure value (combined exposure), which should be considered in the risk characterization. 

The risk characterization is carried out by quantitatively comparing the outcome of the hazard (effects assessment) to the outcome of the exposure assessment, i.e., a comparison of the NOAEL, or LOAEL, and the exposure estimate. The ratio resulting from this comparison is called the Margin of Safety (MOS) (MOS = N(L)OAEL/Exposure). This is done separately for each potentially exposed population, i.e., workers, consumers, and man exposed via the environment, and for each toxicological endpoint, i.e., acute toxicity, irritation and corrosion, sensitization, repeated dose toxicity, mutagenicity, carcinogenicity, and toxicity to reproduction. 

Attempts to reduce the uncertainty of particular aspects of the risk assessment process do not succeed in decreasing the uncertainty attached to the overall assessment. For example, great efforts are put into standardizing methods of testing, so that a test will produce the same result time after time, from laboratory to laboratory.4 This increases the certainty as to whether a chemical has a particular hazardous property or not and enables the concentration at which it has an adverse effect to be precisely defined. However, precision and certainty are only achieved because the property is defined in relation to the very particular conditions under which the test is carried out it is doubtful that these conditions are representative of the situations that are of concern, in which heterogeneous wild animal or human populations are exposed to chemicals. We may be sure of the result of the test, but very uncertain as to its relevance with respect to the risks we are trying to assess. 

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