Case study exposure characterization

Case Study Probabilistic Characterizations of the Doses from Exposure 284... 

CASE STUDY PROBABIUSTIC CHARACTERIZATIONS OF THE DOSES FROM EXPOSURE... 

The distribution of trichloroethylene in humans after oral exposure is poorly characterized. Case studies of oral exposure have found measurable levels in the blood (Perbellini et al. 1991). 

It is interesting to mention that USEtox is mainly a tool for LCIA studies where characterization factors are obtained for a wide list of substances. However, the model also provides intermediate output parameters (e.g., intake doses, concentrations in environmental compartments, substance exposure) that can be used for risk assessment studies. This was the case in the present study comparing the values from USEtox with reference limit values. 

Most of the toxic effects of vanadium compounds result from local irritation of the eyes and upper respiratory tract rather than systemic toxicity. The only clearly documented effect of exposure to vanadium dust is upper respiratory tract irritation characterized by rhinitis, wheezing, nasal hemorrhage, conjunctivitis, cough, sore throat, and chest pain. Case studies have described die onset of asthma after heavy exposure to vanadium compounds, blit clinical studies to date have not detected an increased prevalence of asthma in workers exposed to vanadium. 

No acute-, intermediate-, or chronic-duration oral MRLs were derived for barium because of limitations of the studies evaluating oral exposure to barium for such durations. Case studies of acute exposures in humans did not provide adequate characterization of the doses associated with adverse health effects and acute-duration animal studies did not provide sufficient data to identify a target organ. 

The system consists of two parts. The first part involves using either available information from the drug development process or making reasonable speculations to characterize the potential hazards to the workforce from exposure to the compounds. The second step involves using that information to assess the risk of exposure and recommend controls that prevent exposure. There is more than one suitable control method that can control most exposure points, and several examples have been provided. Finally, case studies have been provided to demonstrate the effectiveness of some of these control methods. 

Renal Effects. Case studies were located regarding renal effects in humans after oral exposure to chromium(VI) compounds. Acute renal failure, characterized by proteinuria, hematuria, followed by anuria, developed in a chrome plating worker who had accidentally swallowed an unreported volume of a plating fluid containing 300 g chromium trioxide/L. He was treated by hemodialysis (Fristedt et al. 

Annex 1 provides a case-study of a qualitative characterization of uncertainties in an exposure assessment. Table A1.2 in Annex 1 details the evaluation throughout the three-dimensional characteristics. Included is an overall conclusion on sensitivity—that is, those aspects that have the most significant impact on the outcome of the assessment, as better data collected on these features would considerably reduce the measure of uncertainty. An example of the overall conclusion is given in section A 1.5 of Annex 1. The main uncertainties identified in the assessment are tabulated, as illustrated in Table 5, and a brief explanation of the weights given to them in reaching an overall conclusion is provided. In addition, a textual description of the qualitative characterization of tabular output should include an indication of overall uncertainty, based on the collective impact of each of the sources. 

The case-study supposes (1) full agreement about characterization of the issue among stakeholders, (2) well defined objectives of the assessment and (3) adequate communication and understanding by stakeholders and peers of the purpose of the exposure assessment, which is anticipated to be characteristic of circumstances for most regulatory applications. 

This case-study addresses the problem of defining, characterizing and propagating uncertainty in an exposure model. Uncertainty analysis is used to assess the impact of data precision on model predictions. A common complaint associated with worst-case approaches to risk assessment is that the use of highly conservative values for each input variable results in significant overestimation of actual risk and/or exposure factors. 

CHARACTERIZING DOSE AND RISK IN A CUMULATIVE ASSESSMENT 277 CASE STUDY 280 Case Study Defining Risk 280 Case Study The Dose-Response Relationship 280 Case Study Using the Margin of Exposure to Characterize the Risk 281 Case Study Benchmark Doses 282 Case Study Margins of Exposure 284... 

Risk characterization is a combination of two components (1) a toxicological characterization of each pesticide having a common mechanism for the given toxicity endpoint and exposure duration, and (2) the exposure characterization for a specified population. Exposure characterization is illustrated in the case study and is also discussed later in this chapter. The methodology for combining the exposure characterization with the toxicological information to form the dose and risk characterizations is discussed in the remainder of this section. 

The toxicological characterizations (EDio, BMD, TEF and TED), the calculation of the doses from exposures, and the risk characterization (Total MOE) are illustrated in the case study that follows. 

CASE STUDY USING THE MARGIN OE EXPOSURE TO CHARACTERIZE THE RISK... 

In Section 1.2.9, a case study was presented on how EPR was used to identify and characterize the NO2 radical supported on an oxide surface. To further illustrate the generic nature of this analytical approach in EPR to the investigation of the properties of surface radicals, the case of CO2 adsorbed on an MgO surface will be presented. This radical can be easily formed by exposure of CO2 to MgO containing excess surface electron trapped species (that is the (H )(e ) centers discussed in the previous section). Although it has been studied on different oxides over the years [38, 39], a study by Chiesa and Giamello [40] demonstrates the wealth of information that can be obtained from the powder EPR spectrum. The EPR spectrum for the surface (MgO) supported C02 species is shown in Figure 1.19. 

There are sufficient data to characterize the acute and chronic toxicity of propylene glycol in laboratory animals, including nonhuman primates. In humans, information on toxicity is limited to medical case studies. However, because of the similarities in the toxicokinetic profile of propylene glycol across species, the toxicity data from the animal studies can be extrapolated to human exposures. 

Williams, P. R., and Paustenbach, D. J. (2005). Characterizing historical industrial hygiene data A case study involving benzene exposures at a chemical manufacturing facility (1976-1987). 7 Occup Environ Hyg 2, 341-350. 

A modifying factor (MF) may also be applied to the calculation of an RfD to account for uncertainties that are not specifically addressed by the individual UFs. For example, deficiencies in the key study, such as a statistically minimal sample size or poor exposure characterization, may warrant the use of an MF greater than 1. Conversely, allowance is made for the use of an MF of less than 1 if the use of the standard default UFs results in a RfD that, in the professional judgment of the risk assessors, is excessively low this might occur in the case of essential elements. If all the uncertainties in the derivation of a RfD are addressed by the use of the five Uncertainty Factors, then the default value for the MF is 1. 

This review provides an up-to-date overview of the application of analytical procedures based on MS for the characterization of organic natural materials in archaeological and historical objects. Applications that feature the use of gas chromatography/mass spectrometry (GC/MS), Py-GC/MS, high performance liquid chromatography combined with mass spectrometry (HPLC/MS), and direct MS analysis such as matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), electrospray ionization mass spectrometry (ESI-MS), and direct exposure mass spectrometry (DE-MS) are sununarized to highlight the different information provided by each of the various analytical approaches. Case studies and examples are also presented and include a description of the molecular markers and of the molecular profiles that are used to identify the original materials. 

This section presents three case examples of site-based lead exposure characterizations for subsequent risk assessment purposes. The case studies are based on research where environmental media-specific levels of Pb were determined as part of the epidemiological and statistical designs. For purposes of this section, such two-part case studies are desirable for, first, quantifying baseline exposure characterizations and eventual baseline human health risk characterizations and, second, for identification of which... 

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