HAZARD AND EXPOSURE

It should be possible to determine the hazardous properties of a substance from its molecular structure. The properties of pharmaceuticals are almost always first predicted using computational techniques such as Quantitative Structure-Activity Relationships9 (QSAR) before further product development [39]. Most industrial chemicals have been produced before these in-silico tools were available or readily accessible10. Of course, our current knowledge and understanding of science, let alone that of a risk assessor, also limits the application of such methods. 

9 A chemical structure can be used to predict its interaction with environmental media and biological systems. Even simple physical chemistry can accurately predict the persistent and bioaccumulative properties of certain types of chemical [86]. Equally, certain hazardous properties can be qualitatively predicted by comparing a molecular structure with similar substances with known hazard profiles [87], Many developments have been achieved using actual computational techniques (e.g., QSAR) to quantitatively evaluate the toxic properties of substances, particularly pharmaceuticals (see [88, 89]). 

10 Computer programmes have recently become available to companies to carry out such exercises at relatively low cost (e.g., [87, 90]). 

In practice, while hazard identification forms the basis of hazard assessment, hazard characterisation serves in analysing data when establishing whether a substance is dangerous or 

11 This book uses the term dangerous but this term will be changed in the REACH Regulation to hazardous by the Classification, Labelling and Packaging Regulation 1272/2008 in December 2010. 

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Once the hazard and exposure assessments ate complete for any specific hazard, it is relatively simple to determine how many people will be affected and the severity of the effect (i.e., the risk). It is considerably more difficult to decide whether these risks are warranted compared to the benefits. This is particularly true if the risks are uncertain, involuntary, or not understood by those at risk if those at risk are not primarily those who benefit or if alternatives are unknown, uncertain, or impractical. The process is complex because the goals are multiple and frequently contraindicating. 

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. ... 

The degree of confidence in the final estimation of risk depends on variability, uncertainty, and assumptions identified in all previous steps. The nature of the information available for risk characterization and the associated uncertainties can vary widely, and no single approach is suitable for all hazard and exposure scenarios. In cases in which risk characterization is concluded before human exposure occurs, for example, with food additives that require prior approval, both hazard identification and hazard characterization are largely dependent on animal experiments. And exposure is a theoretical estimate based on predicted uses or residue levels. In contrast, in cases of prior human exposure, hazard identification and hazard characterization may be based on studies in humans and exposure assessment can be based on real-life, actual intake measurements. The influence of estimates and assumptions can be evaluated by using sensitivity and uncertainty analyses. - Risk assessment procedures differ in a range of possible options from relatively unso-... 

Plants used to produce PRPs should be amenable to confinement . Isolation distances were increased, and the cultivation of food and feed crops following a PRP crop was discouraged. New hazard and exposure data for human and livestock health assessment may also be required from PRP-containing traditional food or feed crops prior to the approval of field trials. Exposure risk concerns the potential for PRPs to be present in human food or animal feed, and where exposure can occur, what mechanisms are used to limit biological activity. Hazards included direct toxicity and allergenicity in humans or animals as well as hazards presented by the coproduct streams that result from processing. These latter requirements could place a major burden on proponents to prove their materials are safe prior to even confined field trials. 

In many cases, hazard based substitution eliminates the need for notoriously difficult exposure assessment. Persistence and bioaccumulation potential are surrogate measures of both hazard and exposure that can be applied quickly to all chemicals In order to identify those of greatest concern. 

Another model, used in the USA, is the OASYS Pollution Prevention Optional Analysis System, developed by the Toxic Use Reduction Institute. Technologies are assessed on a variety of hazard criteria, including acute and chronic human toxicity, physical properties, aquatic impacts, persistence/bioaccumulation, atmospheric releases, disposal, chemical properties, energy/resource use, product hazard and exposure potential. Alternatives are rated to... 

Risk characterization is thus the step in the risk assessment process where the outcome of the exposure assessment (e.g., daily intake via food and drinking water, or via inhalation of airborne substances) and the hazard (effects) assessment (e.g., NOAEL and tolerable intake) are compared. If possible, an uncertainty analysis should be carried out, which produces an estimation of the risk. Several questions should be answered before comparison of hazard and exposure is made ... 

Linch AL, O Conner GB, Barnes JR, et al Methylene-bis-orfl5o-chloroaniline (MOCA) Evaluation of hazards and exposure control. Am Ind Hyg Assoc J 32 802-819, 1971... 

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. 

Risk characterization (also referred to in the CTSA process as risk integration) is the integration of hazard and exposure information to quantitatively or qualitatively assess risk. 

Hazard or dose-response assessment the attempt to assemble the hazard and exposure information along with mathematical models to estimate an upper bound on the carcinogenic risk at a given dose. 

Change can be expected in almost every aspect of both the applied and the fundamental aspects of toxicology. Risk communication, risk assessment, hazard and exposure assessment, in vivo toxicity, development of selective chemicals, in vitro toxicology, and biochemical and molecular toxicology will all change, as will the integration of all of these areas into new paradigms of risk assessment and of the ways in which chemicals affect human health and the environment. 

Doxsee and Hutchison (2004, p. 51) further conceptualize risk of adverse effects from chemicals as a function of intrinsic hazard and exposure, which they summarize in the following equation ... 

Risk evaluation in the assessment process focuses on weighing the health and environmental threats posed by an identified hazard. First, the possibility and probability that a person will actually experience an adverse effect as a result of the existence of the environmental hazard and exposure to it must be weighed and, secondly, the number of persons who might be exposed must be considered. 

Environmental risk or environmental impact is an essential concept of green engineering (http //www.apa.govi ogpugreenengmeaning).1 There are numerous literature references on environmental risk assessment and some are included in the list of references in this chapter. Risk assessment considers the extent of harm a chemical and its uses pose to human health and the environment. Mathematically, it is expressed as a function of hazard and exposure ... 

As defined previously, risk is a function of hazard and exposure. In the environmental risk context, hazard is a function of toxicity which is affected by physical/chemical and environmental fate properties and hence chemistry. Green chemistry reduces the risk or environmental impact of processes or products by focusing on the hazard component. 

Fig. 6.2. Green engineering addresses both the hazard and exposure components of the risk equation. (P/C = physical chemical properties).

Bryan TR, Ross RH. 1988. Chemical scoring system for hazard and exposure identification. J Toxicol Environ Health 1 119-134. 

Risk assessment evaluates risk in terms of hazard and exposure, but reference to risk levels must account for different perceptions of risk as well as scientific uncertainties in risk assessment. In short, this research project considers the importance of social and institutional processes in influencing risk perceptions and risk acceptability. This book therefore takes a constrained relativist approach by incorporating risk perceptions in the research framework. An unconstrained relativist perspective would imply that no scientific study is reliable or robust. By contrast, a constrained relativist approach can provide a useful basis for examining the different social and cultural factors involved in regulatory risk management. 

Because risk levels depend on how the risk (i.e., hazard and exposure) is perceived by individuals or social groups (Section 1.2), any method... 

P. Frier, Hazard and Exposure Considerations Related to Chemical Risk Assessment, Greener Management International, 2003, 41, 47. 

Cumulative Assessment Group (CAG) A subset of chemicals selected from a common mechanism group for inclusion in a refined quantifative estimate of risk. The chemicals in the CAG, as well as their pathways/routes and pesticide uses, are judged to have a hazard and exposure potential that could result in the expression of a cumulative risk. Thus, negligible contributors are not included in quantifying the risk (USEPA, 2002). 

Risk assessment therefore reqnires knowledge of both the hazard of a chemical and the purpose for which it is being used. A highly hazardous substance presents a very low risk if it is securely contained with no likely exposure. Conversely, a substance of relatively low hazard may present nnacceptable risks if extensive exposnre can occur. Both hazard and exposure must be considered before the risk can be adequately assessed. 

Risk, in its scientific meaning, has two components, namely hazard and exposure. To swim in an ocean is hazardous, but people living inland are never exposed to swimming in the ocean. This means that their personal risk of being harmed by the ocean is very small. 

To encourage industry participation in this voluntary pilot project, the Agency has provided regulatory flexibility in the form of certain expedited reviews of PMNs. For purposes of this voluntary pilot project, EPA implemented a program leading to the opportunity for simultaneous submissions of Test Market Exemption applications and PMNs on chemical substances for which the submitter demonstrates the application and use of the P2 Framework or other scientifically acceptable hazard and exposure... 

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