Exposure and Toxicity

Smelters are not the principal source for emitting arsenic into the air the burning of coal is. Burning of coal releases from 0.08-16 pg arsenic per gram of coal [15]. Estimates based on annual consumption of 400 million tons of coal by power plants is approximately 3,000 tons per year [11]. 

The other principal source of arsenic emission to the atmosphere in the US is cotton ginning dust. Cotton ginning dust and the combustion of cotton gin wastes have been reported as creating significant concentration of arsenic in the air downward from these operations [10]. It has also been reported that a seasonal variation of arsenic concentration in the atmosphere is observed which coincides with the cotton farming activities of harvesting and ginning [3]. 

The use of arsenic as a medicine, although practiced for hundreds of years reached a peak in the mid to late 1800 s. Sowler s solution, containing arsenic trioxide at 10 mg/ml was prescribed for symptomatic relief of many conditions, ranging from acute infections to epilepsy, asthma, and chronic recurring skin eruptions, such as eczema and psoriasis [10]. Many patients received arsenic for months and years and it was in such patients that the consequences of long-term administration of arsenic were first recognized. 

Arsenic and all of its compounds are poisonous. Subacute arsenic poisoning usually occurs when a victim is exposed to amounts of arsenic sufficient to cause symptoms but inadequate to make the victim collapse immediately. The victim may go weeks with gradually increasing signs and symptoms related to several organ systems and giving the appearance of a progressive chronic disease state. If death occurs it appears to be due to a natural disease. This appearance has contributed to the popularity of arsenic in homicides. 

Acute arsenic poisoning usually occurs through ingestion of contaminated food and drink. The signs and symptoms are variable and depend on the form and amount of arsenic, the age of the patient, and other factors. The major characteristics of acute arsenic poisoning are profound gastrointestinal damage and cardiac abnormalities. 

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Although biphenyl and the terphenyls fall under the ha2ardous chemical criteria of the OSHA Ha2ard Communications Standard, the products themselves are fairly low in toxicity and do not constitute a serious industrial ha2ard. Some relevant exposure and toxicity data are summari2ed in Tables 5 and 6. 

This second volume of the book presents the results obtained during the RISKCYCLE project, paying special attention to a set of selected additives in the diverse industrial sectors (i.e., PFOS, DEHP, Pb). Different methodologies have been used to analyze aspects such as the fate, human and environmental exposure, and toxicity of these compounds. Case studies have been developed to assess their risk in developing countries such as China or Vietnam. The findings have been presented in the different RISKCYCLE workshops as well as at the final conference in Dresden. 

Information regarding emission, fate, exposure, and toxicity of these chemicals is scarce, especially at the end of the product s life. 

The second innovative peculiarity is the application of HRA-oriented in vitro investigation a human in vitro model has been used to obtain more information on the effect of leachate exposure and toxicity accounting of not only the toxicity of hydrophilic and lipophilic compounds but also the effects of whole leachate as a complex mixture. 

Such studies provide important information for a better interpretation of the toxicity observed in animals, and aid in the selection of not only the proposed initial human dose but of the dose-escalation scheme and the frequency of dosing in the clinical trial(s). Further, once such exposure data are available in humans, the data can be used to better correlate the human and animal findings. Toxicity studies should be performed in the same species used to assess exposure. Often, exposure and toxicity are measured in the same study, particularly when nonrodents are used. 

New aspects of CAP exposure and toxicity arose when residues of CAP metabolites were detected in kidney, liver and muscles of chickens that had received oral doses of CAP 12 days before being slaughtered139. Of these, nitroso-CAP, dehydroCAP and dehydroCAP base [l-(p-nitrophenyl)-2-amino-3-hydroxypropanone] appear of particular toxicological importance. The results, however, should be confirmed since it is quite unexpected that a reactive compound such as nitroso-CAP can be detected in organs 12 days after dosing with CAP. 

They explained that improved analysis of exposures and toxicity in non-temperate biomes would be needed for such an exemption. 

Stewart RD, Gay HH, Erley DS, et al Human exposure to carbon tetrachloride vapor-relationship of expired air concentrations to exposure and toxicity. J Occup Med 3 586-590, 1961... 

Toxicology. In experimental animals, 2,4,6-trichlorophenol causes toxic effects to the liver and hematologic system and cancer. There is no reliable information regarding exposure and toxic effects in humans. 

Toxicology is the science that studies the harmful effects chemicals can have on the body. All chemicals affect man to some degree, depending on the time of exposure, concentration, and human susceptibility. One chemical may only cause a slight rash or dizziness while another may result in cancer or death. It is the degree of exposure and toxicity that are of practical concern. 

As discussed above, the risk of chemicals in the environment is dependent on both exposure and toxicity. Pathways through which organisms in the environment are exposed to chemicals are therefore key determinants of how safe (and therefore, how green ) a chemical is, and must be considered in moving towards a reduced risk or hazard approach to the production and use of chemicals. Fate in the environment is the principal determinant of exposure and designing chemicals for reduced hazard and risk to the environment involves consideration of processes that affect the chemical in the environment, in addition to toxicity. Assessment of environmental fate, including design of chemicals for nonpersistence, is discussed in detail in Chapter 16. 

The following discussion highlights the availability, or absence, of exposure and toxicity information applicable to human health assessment. A statement of the relevance of identified data needs is also included. In a separate effort, ATSDR, in collaboration with NTP and EPA, will prioritize data needs across chemicals that have been profiled. 

Highlighted the kinetic, metabolic, exposure, and toxicity differences of a preformed or synthetic metabolitefs) compared to that... 

The importance of having good data on both exposure and toxicity in order to assess worker hazard has been discussed. It appears that the state of the art is not yet well enough defined to enable a definitive model to be constructed. However, this approach is useful in pointing to areas where more information is necessary to enable viable models to be developed. 

PBDE PBDE congeners in blood and breast milk Emerging exposure and toxicity database Biomarker results useful for demonstrating need for research and establishing reference range... 

Our ENVIRONMENT exposes us daily to a wide variety of xenobiotics in our food, in the air we breathe, or as a result of industrial exposure and toxic wastes. However, despite this exposure, most of us are living long, healthy lives. Certainly individual variation could account for some of the variability in resistance to disease, but other factors are undoubtedly involved. According to a growing body of evidence, diet may be extremely important in increasing resistance to chronic disease. One is tempted to speculate, or hope, that improved dietary habits could improve individual resistance to chemically induced chronic disease. 

The review presented in the previous sections shows an enormous diversity in risk assessment methods and procedures for chemical mixtures. This diversity is characteristic for the current state of the art. The awareness that mixtures may cause risks that are not fully covered by single compound evaluations is growing, but the knowledge required to accurately assess the risks of chemical mixtures is still limited. The scientific community is attempting to unravel the mechanisms involved in mixture exposure and toxicity, and over recent decades, a multitude of new techniques to assess mixture risks have been developed. However, a comprehensive and solid conceptual framework to evaluate the risks of chemical mixtures is still lacking. The framework outlined in Section 5.4 can be considered a first step toward such a conceptual framework. The framework recognizes that the problem definitions vary greatly (between protective and retrospective assessments, for humans and ecosystems), and that each question has resulted in a different type of approach. 

Invertebrates had been thought to have poor capability to biotransform many POPs, as shown by experiment [186-188]. This lack is likely from low CYP abundance and activity. Chirahty has shown that while it is likely that most aquatic invertebrates do indeed lack the capacity to biotransform POPs, some species are capable of metabolizing some POPs stereoselectively. This finding is significant, as invertebrates are a major component of lower food webs, and bioaccumulation of nonracemic POPs results in more significant enantiomer-specific exposure and toxicity to predator organisms, including humans. 

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