Health risk assessment hazard characterization

Leung, W.W. and D.J. Paustenbach. 1995. Physiologically based pharmacokinetic and pharmacodynamic modeling in health risk assessment and characterization of hazardous substances. Toxicol. Lett. 79 55-65. 

Risk assessment is an empirically based process that estimates the risk of adverse health effects from exposure of an individual or population to a chemical, physical, or biological agent or property. The health risk assessment process involves the following steps hazard identification, effects assessment (dose-response assessment), exposure assessment, and risk characterization (Van Leeuwen and Vermeire 2007). 

Health risk assessment is defined as tlie process or procedure used to estimate tlie likelihood that humans or ecological systems will be adversely affected by a chemical or physical agent under a specific set of conditions. Tlie health risk evaluation process consists of four steps hazard identification, dose-response assessment or liazard assessment, exposure assessment, and risk characterization. 

Human health risk assessments with chemicals and other agents (biological, physical) typically follow a paradigm that involves four steps - hazard identification, dose-response assessment, exposure assessment, and risk characterization. The process was recommended by the US National Research Council in the 1980s, and is usually applied to a single agent and exposures associated with one or more routes (oral, dermal, inhalation). This has been more recently referred to as aggregate exposure and risk assessment. 

Risk assessment is a process where the magnitude of a specific risk is characterized so that decision-makers can conclude whether the potential hazard is sufficiently great that it needs to be managed or regulated, reduced or removed. The National Research Council (NRC, 1983) of the National Academy of Sciences (NAS) first described the process of human health risk assessment, with an update in 1994 and 1996, as a four-component paradigm (i.e., hazard identification, dose-response assessment, exposure assessment, and risk characterization), with risk communication as a fifth area of study. The first four components are described briefly below. 

The four major steps in a health risk assessment are hazard identification, dose-response assessment, exposure assessment, and risk characterization. 

As discussed in the previous problem set, the four major steps in a health risk assessment are hazard identification, dose-response assessment, exposure assessment, and risk characterization. A health risk assessment initially involves the identification of human health effects attributed to exposure to a chemical, usually on a continuous basis. A dose-response assessment determines how different levels of exposure to a hazard or pollutant affect the likelihood or severity of the health effects. An exposure assessment determines the extent of human exposure. These are combined to provide a risk characterization value. 

Health risk assessment has 4 major components hazard identiHcation dose-response assessment exposure assessment and, risk characterization. 

Risk assessment in human populations is broadly defined within the vocabulary of the National Academy of Science/National Research Council (NAS/ NRC) (1983) monograph on the topic as [quantitative] characterization of the potential adverse health effects from quantified exposures of humans to environmental hazards. In keeping with the NRC report s use of the term, both qualitative and quantitative risk assessments are considered when dealing with lead contamination and adverse effects in this text, although the most useful information emerged when empirical determination or modeling estimations produced a numerical outcome. Part 4 (Chapters 20—24) of this monograph presents the topic of human health risk assessment in detail. 

Part 4 continues with lead-specific discussions of the four components of a human health risk assessment as structurally articulated in 1983 by the NAS/NRC (1983) Chapter 21, human health hazard characterization for lead and diverse human populations Chapter 22, dose—toxic response relationships for lead in humans Chapter 23, illustrative uses of case- or setting-specific lead exposure characterizations and. Chapter 24, the last part of health risk assessment, the overall final and most quantitative step in actualizing (in a relative sense) the estimates of risk outcomes. 

Noted earlier in passing, lead is different from many toxic substances subjected to human health risk assessment methods in that the toxicant not only poses risk of disease but causes actual disease as well. What is more, this disease-producing substance works to do so in human populations as well as in experimental animals. This propensity of lead is amply characterized in a huge database that permits us to discover this duality and to integrate each form with the other. There are many hundreds and thousands of environmental contaminants which are not well characterized, so that we are left with quantifying hazards to human health in the form of calculated probabilities for harm using formulaic methodologies. 

This chapter s characterization of lead as a neurotoxic hazard does not include detailed dose—response relationships with various levels of biomarkers such as PbB linked to various neurotoxic outcomes. The topics of dose/ exposure metrics and defining full-spectrum dose—response relationships are presented in the next part, the section dealing with the elements of human health risk assessment for environmental lead. Here, for ease of discussion, only a broad yardstick is provided for toxic lead exposures. Specifically, general PbB ranges associated with the various categories of lead neurotoxicity, especially in children, are noted. 

GENERAL ISSUES FOR HAZARD CHARACTERIZATION LEAD AS THE PROTOTYPIC MODEL FOR HUMAN HEALTH RISK ASSESSMENT... 

The time-dependent human health hazard characterization for lead is best summarized by chronological blocks of time and those adverse health effects that were considered of medical or scientific importance. Associated with the various levels of adverse health effect severity are body lead burdens or dose. The combination of these dose ranges, whether measured at the time or retroactively imputed as likely lead doses given current knowledge, defines the dose—response relationship, also called the dose—effect severity relationship. This topic as the third component of health risk assessment is addressed in Chapter 22. 

The second element of health risk assessment for lead is the identification of dose—response relationships for the various adverse health effects noted in the previous chapter. Dose—response relationships, like health hazard characterizations, are general in nature and independent of site-specific lead exposure scenarios. 

Lin, Y.C., Lee, W., Chend, S.J., Chang-Chien, G.P., Tsai, P.J. (2008). Characterization of PAHs exposure in workplaee atmospheres of a sinter plant and health-risk assessment for sintering workers. Journal of Hazardous Materials, 158, 636-643... 

Hazard identification involves gathering and evaluating data on the types of health injury or disease that may be produced by a chemical and on the conditions of exposure under which injury or disease is produced. It may also involve characterization of the behavior of a chemical within the body and the interactions it undergoes with organs, cells, or even parts of cells. Hazard identification is not risk assessment. It is a scientific determination of whether observed toxic effects in one setting will occur in other settings. 

Most human or environmental healtli hazards can be evaluated by dissecting tlie analysis into four parts liazard identification, dose-response assessment or hazard assessment, exposure assessment, and risk characterization. For some perceived healtli liazards, tlie risk assessment might stop with tlie first step, liazard identification, if no adverse effect is identified or if an agency elects to take regulatory action witliout furtlier analysis. Regarding liazard identification, a hazard is defined as a toxic agent or a set of conditions that luis the potential to cause adverse effects to hmnan health or tlie environment. Healtli hazard identification involves an evaluation of various forms of information in order to identify the different liaz.ards. Dose-response or toxicity assessment is required in an overall assessment responses/cffects can vary widely since all chemicals and contaminants vary in their capacity to cause adverse effects. This step frequently requires that assumptions be made to relate... 

Risk characterization is the last step in the risk assessment procedure. It is the quantitative or semi-quantitative estimation, including uncertainties, of frequency and severity of known or potential adverse health effects in a given population based on the previous steps. Risk characterization is the step that integrates information on hazard and exposure to estimate the magnitude of a risk. Comparison of the numerical output of hazard characterization with the estimated intake will give an indication of whether the estimated intake is a health concern. ... 

In this chapter the risk assessment is briefly introduced. Risk assessment is divided into four steps hazard identification, hazard characterization, exposure assessment, and risk characterization. This chapter also highlights five risk and life cycle impact assessment models (EUSES, USEtox, GLOBOX, SADA, and MAFRAM) that allows for assessment of risks to human health and the environment. In addition other 12 models were appointed. Finally, in the last section of this chapter, there is a compilation of useful data sources for risk assessment. The data source selection is essential to obtain high quality data. This source selection is divided into two parts. First, six frequently used databases for physicochemical... 

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. 

For both human health and the environment, the risk assessment process includes (i) an exposure assessment, (ii) an effect assessment (hazard assessment and hazard characterization -addressed in detail in Chapter 4), and (iii) a risk characterization (addressed in detail in Chapter 8). As a part of the effect assessment, classification and labeling of the substance according to the criteria laid down in Directive 67/548/EEC (EEC 1967) is also addressed (Section 2.4.1.8). 

The aim of the risk characterization of a chemical substance under evaluation is to integrate the hazard assessment and exposure assessment in order to evaluate the qualitative and quantitative probability for a health risk likely to occur in a given human population due to actual or predicted exposure to that specific chemical as well as the seriousness of any health risk. 

Hazard identification is the process of collecting and evaluating information on the effects of an agent on animal or human health and well-being. In most cases, this involves a careful assessment of the adverse effects and what is the most sensitive population. The dose-response assessment involves evaluation of the relationship between dose and adverse effect. Typically, an effort is made to determine the lowest dose or exposure at which an effect is observed. A comparison is often made between animal data and any human data that might be available. Next is exposure assessment, in which an evaluation of the likely exposure to any given population is assessed. Important parameters include the dose, duration, frequency, and route of exposure. The final step is risk characterization, in which all the above information is synthesized and a judgment made on what is an acceptable level of human exposure. In the simplest terms, risk is the product of two factors hazard and exposure (i.e. hazard x exposure = risk). In real risk assessments, all hazards may not be known and exposure is often difficult to quantify precisely. As a result, the calculated risk may not accurately reflect the real risk. The accuracy of a risk assessment is no better than the data and assumptions upon which it is based. 

The first step in risk assessment is to gather health-related information associated with an exposure. Ideally, hazard identification starts before there is significant use of the agent. The structure of the compound is compared with that of compounds with known toxicity profiles. Cell-based studies are often performed to screen for toxicity. Finally, animal bioassays and human studies are performed to characterize and develop a toxicity profile. Multiple health-related endpoints are evaluated to determine if the compound is associated with adverse effects. Advantages of animal studies include experimental control and accurate knowledge of the dose. 

The second objective of the hazard assessment concerns characterization of the identified hazards of a particular substance. Under REACH this means that the registrant must define so-called derived no-effect levels., abbreviated DNELs. With respect to human health, these values constitute exposure levels above which humans should not be exposed and below which risks for humans are considered controlled. The DNEL derivation is a complex process which comprises several conversion steps and the application of different assessment factors. In the case of reproductive toxicity, the registrant derives separate DNELs with respect to developmental toxicity on the one hand and to impairment of sexual function and fertility on the other hand. 

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