Hazard extrapolation

Chemical exposure, electrochemical process industries, 9 646-647 Chemical exposure hazards, extrapolating, 25 228... 

The NRC document calls for hazard identification, dose-response assessment, exposure assessment, and risk characterization. In an effort to place descriptive experimental toxicity results in a clearer perspective and place more emphasis on evaluation, this outline deviates slightly from the NRC document and calls for hazard evaluation, hazard extrapolation, exposure assessment and risk characterization. In addition, a few comments on risk acceptability are given. Exposure assessments have been adequately discussed elsewhere in this symposium and will be discussed here only as they relate to hazard identification, evaluation, extrapolation and risk characterization. 

Hazard extrapolation is used here to mean extrapolation both from the observed effect levels to non-tested levels within the tested... 

From all what is described above, it should be difficult to make accurate and reliable cycle-life predictions, hi fact, hazardous extrapolations can be avoided providing some basic rules are followed, and good approximations of some of the parameters can be made. The following points are obvious ... 

The frequency analysis step involves estimating the likelihood of occurrence of each of the undesired situations defined in the hazard identification step. Sometimes you can do this through direct comparison with experience or extrapolation from historical accident data. While this method may be of great assistance in determining accident frequencies, most accidents analyzed by QRA are so rare that the frequencies must be synthesized using frequency estimation methods and models. 

For the overwhelming majority of substances encountered in industry, there are not enough data on toxic responses of humans to permit an accurate or precise assessment of the substance s hazard potential. Frequently, the only data available are from controlled experiments conducted with laboratory animals. In such cases, it is necessary to extrapolate from effects observed in animals to effects likely to occur in... 

Extrapolation of historical data to larger scale operations may overlook hazards introduced by scale up to larger equipment Limitation of fault tree tlieory requires system simplification Incompleteness in fault and event hee analysis Uncertainties in data -... 

When plotting data on two different hazard papers, it is possible that each will result in relatively straight plot. Generally, it doesn t matter which plot is used to interpolate within the range of data. There is an exception however, when extrapolation beyond the given range of data is necessary. In that case, the decision of which plot to use will be determined by the engineer. 

Two main hazards associated with chemicals are toxicity and flammability. Toxicity measurements in model species and their interpretation are largely the province of life scientists. Chemical engineers can provide assistance in helping life scientists extrapolate their resrrlts in the assessment of chemical hazards. Chemical engineers have the theoretical tools to make important contributions to modehng the transport and transformation of chemical species in the body—from the entry of species into the body to their action at the rrltimate site where they exert their toxic effect. Chemical engineers are also more likely than life scientists to appreciate... 

PBPK models improve the pharmacokinetic extrapolations used in risk assessments that identify the maximal (i.e., the safe) levels for human exposure to chemical substances (Andersen and Krishnan 1994). PBPK models provide a scientifically sound means to predict the target tissue dose of chemicals in humans who are exposed to environmental levels (for example, levels that might occur at hazardous waste sites) based on the results of studies where doses were higher or were administered in different species. Figure 3-4 shows a conceptualized representation of a PBPK model. 

Hazard characterization is a quantitative or semi-quantitative evaluation of the nature, severity, and duration of adverse health effects associated with biological, physical, or chemical agents that may be present in food. The characterization depends on the nature of the toxic effect or hazard. Eor some hazards such as genotoxic chemicals, there may be no threshold for the effect and therefore estimates are made of the possible magnitude of the risk at human exposure level (dose-response extrapolation). 

Stages in hazard characterization according to the European Commission s Scientific Steering Committee are (1) establishment of the dose-response relationship for each critical effect (2) identification of the most sensitive species and strain (3) characterization of the mode of action and mechanisms of critical effects (including the possible roles of active metabolites) (4) high to low dose (exposure) extrapolation and interspecies extrapolation and (5) evaluation of factors that can influence severity and duration of adverse health effects. 

NOAEL (no-observed-adverse-effect level) is defined as the highest dose at which no adverse effects are observed in the most susceptible animal species. The NOAEL is used as a basis for setting human safety standards for acceptable daily intakes (ADIs), taking into account uncertainty factors for extrapolation from animals to humans and inter-individual variabilities of humans. The adequacy of any margin of safety or margin of exposure must consider the nature and quality of the available hazard identification and dose-response data and the reliability and relevance of the exposure estimations. In some cases, no adverse endpoint can be identified such as for many naturally occurring compounds that are widespread in foods. In that case, an ADI Not Specified is assigned. ... 

Cl. Dybing, E. et al.. Hazard characterization of chemicals in food and diet dose response, mechanisms and extrapolation issues. Food Chem. Toxicol, 40, 237, 2002. 

Thus both the numerator and denominator terms in Eq. (41), or in Eq. (44), depend on the concentration. Because of this situation empirical extrapolation of D is particularly hazardous (for random coiling polymers). If F2 is known from osmotic or light-scattering measurements at a series of concentrations, extrapolation according to Eq. (44) will be facilitated. (If such measurements have been carried out, however, the molecular weight also will have been determined.)... 

Ihe implementation of the Resource Conservation and Recovery Act (RCRA) and the Comprehensive Environmental Response, Compensation, and Liability Act (Superfund) has underscored a number of the weaknesses in our capabilities to measure the chemical characteristics of wastes. We are now being called upon to identify and quantify with unprecedented sensitivity hundreds of chemicals found in many types of materials within waste sites, near discharges of hazardous contaminants, and in the surrounding environments. Extrapolations from a limited number of measurements must indicate the general environmental conditions near waste sites. The measurements have to be made faster and cheaper than ever before, with the precision and bias of each measurement fully documented. Thus, the technical challenges facing the monitoring community are substantial. 

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. 

Considerable controversy continues to exist as to what concentration of HC1 is hazardous to man. Although numerous studies of the acute effects of HQ have been conducted with rodents, it is questionable whether lethality data from rodents can be directly extrapolated to man because of anatomical differences in the respiratory tract... 

The regional distribution of the DNA adducts in the respiratory tract of diesel exhaust-exposed rats appears to agree with the known deposition pattern of submicron particles, with the highest concentration of adducts in the nasal and the pulmonary tissue (Figure 7) (Bond et al. In Assessment of Inhalation Hazards Integration and Extrapolation Using Diverse Data. 1989, in press). 

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