Health hazard characterization

The physicochemical properties of both PCDD/PCDFs and coplanar PCBs enable these compounds to be readily absorbed by organisms. The high lipid solubility and low water solubility of all congeners lead to the retention of the compounds in 

The main route of excretion is via the faeces (biliary excretion), urine and breast-milk. Excretion through breast-milk results in transfer to breastfed infants, who therefore are highly exposed. There is also transfer across the placenta, thus causing fetal exposure. Perinatal exposure is a major concern with regard to human health effects, even at present background exposure levels. 

The TEF concept has gained wide acceptance and many different schemes have been proposed. Nowadays, the use of the TEFs for dioxins, dibenzofurans and PCBs for humans and mammals suggested by WHO is often recommended (van den Berg et al., 1998). The TEF scheme includes a kind of safety factor, as the TEF values are rounded upwards. 

However, no studies on fetal exposure are available for setting TEFs. Thus there is a need for dose-response studies of the critical effects, based on synthetic mixtures reflecting the human exposure situation. The WHO TEFs for dioxins, dibenzofurans and PCBs for humans and mammals are given in Table 3. 

A plethora of effects have been reported from multiple animal studies following exposure to PCDDs, PCDFs and PCBs. The most extensive data set on dose-response effects is available for 2,3,7,8-TCDD less information is available for the other dioxinlike compounds. Therefore, the focus of the evaluation of the animal data is on the effects of 2,3,7,8-TCDD. 

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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. 

Chapter 21 presents the principal elements of lead health hazard characterization, an assessment of toxic effects in humans and experimental systems done in broader ranging terms. Also included is Pb s characterization using the Bradford Hill criteria for establishing causal relationships in dose—responses. The quantitative aspects of human lead toxicity are set forth in Chapter 22,... 

Chapter 21 achieves this collective human health hazard characterization for lead via a ranking of the component human adverse health effects with respect to thoroughness and quality of the data, the relative sensitivity or ranges of sensitivities of the toxic responses with reference to typical ambient or occupational Pb exposures, the relative gravity of the toxic response in terms of both injury and persistence/irreversibiUty, and reliable supporting evidence from experimental and mechanistic data. 

Human health hazard characterization for lead viewed over an extended time, as seen in other sections, has relied on temporal shifts in the definitions of what can be characterized as an adverse effect, i.e., evidence of organ or tissue damage. Health hazard characterization in Chapter 21 is discussed as the evidence for such assessment currently exists. The current database is obviously more extensive than that of past decades, but one cannot exclude the possibility or even the probability that the database will grow with continued research, particularly given the availability of increasingly more sophisticated tools. Table 20.1 notes that health hazard characterization in Chapter 21 mainly draws from the preceding Pb toxicity chapters. 

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. 

IDENTIFYING RELEVANT TOXIC EFFECTS IN HUMANS FOR LEAD HEALTH HAZARD CHARACTERIZATION... 

TABLE 21.1 Demonstrable Human Health Hazard Characterizations for Lead ... 

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. 

The choice of data to be analyzed for selection of health hazard characterization and applicable dose—responses entails a series of methodological and... 

The first major objective for the inherent safety review is the development of a good understanding of the hazards involved in the process. Early understanding of these hazards provides time for the development team to implement recommendations of the inherent safety effort. Hazards associated with flammability, pressure, and temperature are relatively easy to identify. Reactive chemistry hazards are not. They are frequently difficult to identify and understand in the lab and pilot plant. Special calorimetry equipment and expertise are often necessary to fully characterize the hazards of runaway reactions and decompositions. Similarly, industrial hygiene and toxicology expertise is desirable to help define and understand health hazards associated with the chemicals employed. 

Hazard identification is defined as tlie process of determining whetlier human exposure to an agent could cause an increase in the incidence of a health condition (cancer, birtli defect, etc.) or whetlier exposure to nonliumans, such as fish, birds, and otlier fonns of wildlife, could cause adverse effects. Hazard identification cliaracterizes tlie liazard in terms of tlie agent and dose of the agent. Since tliere are few hazardous chemicals or hazardous agents for wliich definitive exposure data in humans exists, tlie identification of health hazards is often characterized by the effects of health hazards on laboratory test animals or other test systems. ... 

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. 

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. 

OSHA has determined that worker exposure to cotton dust presents a significant health hazard cotimonly referred to as byssinosis ( ). This respiratory disease is characterized by shortness of breath, cough, and chest tightness. Permissible exposure limits have been established for selected processes in the cotton industry 200 ug/ni or less in yarn manufacturing,... 

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). 

Human health hazards assessment is the process of identifying the potential effects that chemical may have on humans who are exposed to it, and of determining the levels at which these effects may occur. Human health toxicity data are compared with data from the exposure assessment module to assess human health risk in the risk characterization module. 

Chemicals risk assessment generally consists of three stages (1) hazard assessment, (2) exposure assessment and (3) risk characterization. However, REACH divides the first stage into four human health hazard assessment, physicochemical hazard assessment, environmental hazard assessment, and persistent, bioaccumulative... 

Risk assessment, a process used to evaluate potential adverse effects on health from human exposure to veterinary drug residues, involves four stages starting from hazard identification and terminating through the hazard characterization and exposure assessment stages to risk characterization. 

Risk characterization, the final stage of risk assessment, sets out to provide a qualitative and/or quantitative estimate, given the uncertainties of assessment, the probability of occurrence, and the severity of known or potential adverse health effects in a given population based on hazard identification, hazard characterization, and exposure assessment. The aim is to characterize the risks to the consumer from residues possibly present in animal products on the basis of use of the substance and particularly the withdrawal period, given that the period of administration and the dosage are predetermined by the objective of effectiveness. 

Consideration of which approach would provide a base for characterizing health hazards associated with drinking waters in the long term. 

CMC information It should contain sufficient detail to assure identification, quality, purity, and strength of the investigational drug. It should include stability data of duration appropriate to the length of the proposed study. FDA concerns to be addressed focus on products made with unknown or impure components, products with chemical structures known to be of likely high toxicity, products known to be chemically unstable, and products with an impurity profile indicative of a health hazard or insufficiently defined to assess potential health hazard, or poorly characterized master or working cell bank. 

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