Risk to exposed population

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. 

Before we plunge into the world of carcinogens, we should note that all of the toxic phenomena we have described exhibit dose-response relationships and that LOAELs and NOAELs can be identified for all. As we shall see in later chapters these quantitative features of toxic phenomena are at center stage when we begin to examine risk to exposed populations. 

The decision maker s problem is to operate within all of the uncertainties inherent in the determination of the adequacy of the qualitative evidence of carcinogenicity to humans and in the quantitative projection of risks to exposed populations and arrive at a reasonable public policy conclusion. One very experienced operative in the field drew the following conclusion regarding the goal of determining the risks to public health from potential carcinogens (47) ... 

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 RfDs and TDIs are often used to establish regulatory standards. Such standards usually specify a limit on the allowable concentration of a chemical in an environmental medium. The process is not difficult to understand. The RfD and its related estimates of population thresholds is a dose, typically expressed in mg/(kg b.w. day), that is considered to be without significant risk to human populations exposed daily, for a lifetime. Consider mercury, a metal for which an RfD of 0.0003 mg/(kg b.w. day) has been established by the EPA, based on certain forms of kidney toxicity observed in rats (Table 8.4). These are not the only toxic effects of mercury, but they are the ones seen at the lowest doses. Note also that we are dealing with inorganic mercury, not the methylated form that is neurotoxic. 

Schantz et al. 1992 Silkworth et al. 1989b Smith et al. 1976 Thomas and Hinsdill 1979 Weber et al. 1985), 2,7-DCDD (Khera and Ruddick 1973 Schwetz et al. 1973), mixed HxCDD (Schwetz et al. 1973), and OCDD (Schwetz et al. 1973). The most common effects were cleft palate, hydronephrosis, impaired development of the reproductive system, immunotoxicity, and death. No studies were located regarding developmental effects in animals after inhalation and dermal exposure. Such studies would be useful for extrapolating the possible risk to human populations exposed environmentally by these routes. 

The calculation to characterize the risk to a population exposed to an event or chemical agent can be divided into the four steps described here. The units correspond to a gaseous chemical emission to the atmosphere posing a risk to a population. 

Large-scale experimental releases of fission product activity are clearly ruled out because of the implications on the safety of the public, described in Section V,F, as are also the smaller scale releases referred to earlier in Section V. Therefore, for verification of our conclusions we have to rely on limited experience from those few accidents that have occurred and that have released fission products (see Section I,D), but much more on our store of knowledge of all the factors involved, i.e., types of reactor accidents (Section II) through fission product release (Section III) and dispersion of a release in the atmosphere (Section IV), to analysis of the radiation and radiobiological hazards and risks to exposed members of the population. In view of these several steps involved in the estimation of hazard, it is reassuring that the many different authors who have written on the topie reach conclusions which are generally similar and differ only in limited areas. 

The severe health effects observed in the Japanese Yusho incident of 1968 were attributed to the ingestion of polychlorinated biphenyls (PCBs). At that time, the forefront of analytical chemistry was represented by the determination of trace components at the parts per million (ppm) concentration level. It was not until about ten years later that analytical methodology was able to detect polychlorinated dibenzofurans (PCDFs) and polychlorinated dibenzodioxins (PCDDs) at concentrations of 10 parts per billion (ppb) or less in the presence of PCBs. The significance of the determinations lies in the assessment of risk to human populations exposed to undegraded PCBs and to mixtures of chemically similar compounds of concern derived from uncontrolled reactions such as might occur when a PCB filled transformer undergoes eventful failure. 

A. Average individual risk (exposed population) is the individual risk averaged over the population that is exposed to risk from the facility... 

The risk to an average individual in the vicinity of a nuclear power plant of prompt fatalities that might result from reactor accidents should not exceed 0.1% of the sum of prompt fatality ri.sks from other accidents to which members of the U.S. population are generally exposed. ... 

The harmful effects of industrial emissions are not confined to the workers but extend beyond the plant boundary line. Chemically-induced diseases among workers exposed to industrial chemicals are a warning sign of the risks to which a larger population is also being exposed usually the chemical hazards are in principle similar in the occupational and general environment. However, occasionally environmental exposures can be qualitatively different from the occupational environment and may also cause deleterious health effects in the general population. 

Dose-Response Evaluation The process of quantitatively evaluating toxicity information and characterizing the relationship between the dose a contaminant administered or received, and the incidence of adverse health effects in the exposed population. From a quantitative dose-respoiise relationship, toxicity values can be derived that are used in the risk characterization step to estimate the likelihood of adverse effects occurring in humans at different exposure levels. 

One should identify exposure pathways that have the potential to expose the same individual or sub-population at the key exposure areas evaluated in the exposure assessment, making sure to consider areas of highest exposure for each patliway for both current and future land-uses (c.g., nemest down-gradient well, nearest dowiuvind receptor). For each pathway, the risk estimates and hazard indices have been developed for a particular exposure area... 

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. 

Maximum Individual Risk The risk to the most exposed individual in an exposed population, such as the person spending the maximum amount of time in a building. 

Average Individual Risk (total population), defined as the individual risk over a predetermined population, whether or not people are actually exposed to the risk. If the population used is large, this risk measure can be deceiving, as it might depict very low risks while limited portions of the population in fact are exposed to high risks. 

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 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. 

The purpose of screening tools, such as MRLs or estimates derived from this approach, is to alert health assessors to substances that may pose risk to the exposed population. In addition, these approaches economize the use of resources by eliminating substances for which there is little likelihood of human... 

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. 

In the case of noncarcinogenic substances, there exists a threshold this is an exposure with a dose below which there would not be adverse effect on the population that is exposed. This is the reference dose (RfD), and it is defined as the daily exposure of a human population without appreciable effects during a lifetime. The RfD value is calculated by dividing the no observed effect level (NOEL) by uncertainty factors. When NOEL is unknown, the lowest observed effect level (LOEL) is used. NOEL and LOEL are usually obtained in animal studies. The main uncertainty factor, usually tenfold, used to calculate the RfD are the following the variations in interspecies (from animal test to human), presence of sensitive individuals (child and old people), extrapolation from subchronic to chronic, and the use of LOEL instead of NOEL. Noncancer risk is assessed through the comparison of the dose exposed calculated in the exposure assessment and the RfD. The quotient between both, called in some studies as hazard quotient, is commonly calculated (Eq. 2). According to this equation, population with quotient >1 will be at risk to develop some specific effect related to the contaminant of concern. 

Many states in the U.S. are currently involved in large scale surveys to measure radon levels in homes in an attempt to assess the environmental risk from radon and radon daughter exposure. Radon daughters deliver the largest radiation exposure to the population and it is estimated that 0.01% of the U.S. population (23,000 persons) are exposed from natural sources to greater than those levels allowed occupationally (4 WLM/yr) (NCRP, 1984). 

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