Exposure to Chemical Substances

Among the 10 million known chemical compounds, there are some 50 000 which are in common use. Workers are usually exposed to several agents simultaneously (their interactions are considered in section 5.3.4.2). In addition, many impurities in workplace air are inherently complex mixtures, which may consist of hundreds of different compounds. Mineral oils and wood dusts are examples of common complex mixtures. 

Occupational and environmental exposure to chemicals can take place both indoors and outdoors. Occupational exposure is caused by the chemicals that are used and produced indoors in industrial plants, whereas nonoccupa-tional (and occupational nonindustrial) indoor exposure is mainly caused by products. Toluene in printing plants and styrene in the reinforced plastic industry are typical examples of the two types of industrial occupational exposures. Products containing styrene polymers may release the styrene monomer into indoor air in the nonindustrial environment for a long time. Formaldehyde is another typical indoor pollutant. The source of formaldehyde is the resins used in the production process. During accidents, occupational and environmental exposures may occur simultaneously. Years ago, dioxin was formed as a byproduct of production of phenoxy acid herbicides. An explosion in a factory in 

Seveso, Italy, caused wide-spread pollution of the industrial site as well as its surroundings. Serious effects of dioxin were detected both in dontestic animals, such as cows and sheep, and in humans, the most serious early effects being a serious skin disease, chloracne, and alterations in the function of the immune system. Follow-up studies have demonstrated that this accident also increased the cancer risk in exposed individuals.  

Outdoor inhalation exposure is mainly due to traffic, energy production, heating, and natural factors such as pollen and mineral dusts. These outdoor sources of pollution also affect indoor air quality. The indoor concentration is typically 20-70% of the corresponding outdoor concentration. Occasionally the indoor concentrations of an external pollutant (especially radon) may even exceed the concentrations outdoors.  

In densely populated areas, traffic is responsible for massive exhausts of nitrous oxides, soot, polyaromatic hydrocarbons, and carbon monoxide. Traffic emissions also markedly contribute to the formation of ozone in the lower parts of the atmosphere. In large cities, fine particle exposure causes excess mortality which varies between one and five percent in the general population. Contamination of the ground water reservoirs with organic solvents has caused concern in many countries due to the persistent nature of the pollution. A total exposure assessment that takes into consideration all exposures via all routes is a relatively new concept, the significance of which is rapidly increasing. 

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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. 

ACGIH maintains annual editions of the TLVs and BEIs which are used worldwide as a guide for evaluation and control of workplace exposures to chemical substances and physical agents. Threshold Limit Value (TLV ) occupational exposure guidelines are recommended for more than 700 chemical substances and physical agents. There are more than 50 Biological Exposure Indices (BEIs ) that cover more than 80 chemical substances. 

FUN tool is a new integrated software based on a multimedia model, physiologically based pharmacokinetic (PBPK) models and associated databases. The tool is a dynamic integrated model and is capable of assessing the human exposure to chemical substances via multiple exposure pathways and the potential health risks (Fig. 9) [70]. 2-FUN tool has been developed in the framework of the European project called 2-FUN (Full-chain and UNcertainty Approaches for Assessing Health Risks in FUture ENvironmental Scenarios www.2-fun.org). 

Modem toxicology has its roots in the occupational environment. The earliest recorded observations relating exposure to chemical substances and toxic manifestations were made about workers. These include Agricola s identification of the diseases of miners and Pott s investigation of scrotal cancer incidence among chimney sweeps. Occupational toxicology, as its name implies, concerns itself with the toxicological implications of exposure to chemicals in the work environment. 

All of these questions are about risks to human health resulting from past, current, and (in the case of the food additive) future exposures to chemical substances. They seem to be highly important questions, and if we are ourselves members of one or more of the exposed populations, we would press scientists and physicians in our public health and regulatory institutions for answers to them. And, if those in authority in those institutions are doing their job, they have programs in place to provide the answers. 

FIGURE 1.1 Human exposure to chemical substances from environmental media and sources. 

Risk assessment is a process by which regulatory and scientihc principles are applied in a systematic fashion in order to describe the hazard associated with human exposure to chemical substances. The information provided by a risk assessment may then be used to regulate the use of the substance, or may not, depending on political, social, economic, and technical considerations in the process of risk management. 

As mentioned previously, the assessment of hazard and risk to humans from exposure to chemical substances is generally based on the extrapolation from data obtained in smdies with experimental animals. In the absence of comparative data in humans, a basic assumption for toxicological risk assessment is that effects observed in laboratory animals are relevant for humans, i.e., would also be expressed in humans. In assessing the risk to humans, an assessment factor is applied to take account of uncertainties in the differences in sensitivity to the test substance between the species, i.e., to account for interspecies variability (Section 5.3). If data are available from more than one species or strain, the hazard and risk assessment is generally based on the most susceptible of these except where data strongly indicate that a particular species is more similar to man than the others with respect to toxicokinetics and/or toxicodynamics. Two main aspects of toxicity, toxicokinetics and toxicodynamics, account for the namre and extent of differences between species in their sensitivity to xenobiotics this is addressed in detail in Chapter 5. 

The Neurophysiology Sensory Evoked Potentials test guideline (OPPTS 870.6855) is designed to detect and characterize changes in the sensory aspects of nervous system function that result from exposure to chemical substances. The techniques involve neurophysiological measurements from adult animals and are sensitive to changes in the function of auditory, somatosensory (body sensation), and visual sensory systems. 

The ingestion of soil is a potential source of human exposure to chemical substances. The exposure is usually expressed as an average amount of soil ingested per unit time (e.g., mg/day). 

Eriksson, M., Hardell, L., Berg, N.O., Mdller, T. Axelson, 0. (1981) Soft-tissue sarcoma and exposure to chemical substances a case-referent study. Br. J. ind. Med, 38, 27-33... 

Occupational exposure to chemical substances almost invariably involves multiple chemicals. That situation may result in PK interactions, which may affect the relationship between the atmospheric concentration of the parent chemical and the associated biomarker concentration (Viau 2002). For example, such an interaction is known to occur between ethylbenzene and the xylene isomers (Jang et al. 2001). Commercial xylene contains about 20% ethylbenzene, which modifies the slope of the relationship between urinary methylhippuric acid (MHA) and airborne xylene concentrations. That kind of interaction is unlikely at the subparts-per-million exposure concentrations seen in the general population. But because the BEI for MHA was obtained from the relationship observed after exposure to commercial xylene, thereby taking the interaction into account, the slope of the relationship cannot be extrapolated to the subparts-per-million range. Similar PK interactions have been observed for other mixtures but only at concentrations nearing or exceeding the occupational exposure limits (Viau 2002), so it would be a priori reasonable to consider extrapolation of the relationship between biomarker concentrations and those of their parent chemicals. For example, Tardif et al. (1991) demonstrated that, provided inhalation exposure to a mixture of toluene and xylene was kept below their airborne occupational exposure limits, there were no PK interactions between the compounds that affected the linear relationship between airborne parent-chemical exposure and urinary-metabolite concentrations. However, such an interaction was apparent at higher concentrations. 

Eriksson M, Hardell L, Berg NO, et al. 1979. Case-control study on malignant mesenchymal tumors of the soft tissue and exposure to chemical substances. Lakartidningen 76 3872-3875. 

MCS is caused by exposure to chemical substances (either a single high-dose exposure or low-dose exposures over a long period of time see entry 2). Often, due to the symptoms and the reactions to various (low dose) chemical substances, it is clear that MCS is at hand, especially when there is also an obvious cause. Of course, the other possible causes of the health situation must be ruled out, since cures exist for many other diseases and naturally the focus must be on those at first. So one ought to conduct all regular tests and studies (consult with your doctor) in order to rule out all other possible physical factors. Some symptoms characteristic of other conditions can resemble the symptoms ofMCS but do not officially fall within them, such as asthmatic diseases (though people with asthma may have developed MCS on the side). 

Dr. William Rea of the Environmental Health Clinic in Dallas, Texas, describes disturbances to the immune system as a result of exposure to chemical substances. He speaks of a Total Body Overload, whereby the body is completely overwhelmed with chemical substances and unable to process them properly. 

Feelings of depression can be a result of exposure to chemical substances, so don t just think that everything is apparently too much for you to handle. Try avoiding chemical substances as much as possible and see what effect it has on your joy of life It s also good to have your blood tested to see if any deficiencies have arisen, in magnesium for example (because this can definitely... 

In case of exposure to chemical substances, it s also very important to try staying as relaxed as possible (stress hormones can burden your body even more) and have faith that you ll soon be okay again. Of course, you should always walk away immediately and protect yourself when something crops up, but panicking (stress ) does not help your (or your partner s) situation. 

Shortness of breath is often a consequence of exposure to chemical substances. Oxygen (see entry 252), can help relieve the problem, but it s always better to prevent exposure to irritants. See also www.the-abc-of-mcs.com under Water Oxygen. ... 

The agency also considered the toxic effects that result from chronic exposure to chemical substances. The results of chronic oral feeding studies of 2-years duration on 220 compounds have shown that only five of the 220 chemicals exhibited toxic effects below 1 mg/kg. All five of the chemicals that were toxic at levels below 1 mg/kg, on a dietary basis, were pesticides, compounds that would, based on their pesticidal activity, be expected to be more toxic than most substances (Frawley, 1967). However, even among these 5 pesticides, none exhibited toxic effects at dietary concentrations below 0.1 mg/kg. 

Workplace exposure to chemical substances and the potential for pulmonary toxicity are subject to regulation by the Occupational Safety and Health Administration under the Occupational Safety and Health Act (OSHA), including the requirement that potential hazards be disclosed on material safety data sheets (MSDS). (An interesting question arises as to whether carbon nanotubes, chemically carbon but with different properties because of their small size and structure, are indeed to be considered the same as or different from carbon black for MSDS pur-oses.) Both government and private agencies can be expected to evelop the requisite threshold limit values (TLVs) for workplace exposure. Also, EPA may once again utilize TSCA to assert its own jurisdiction, appropriate or not, to minimize exposure in the workplace. 

Overview. The Toxic Substances Control Act (TSCA) became effective January 1, 1977. Its major goal is to prevent unreasonable risk of injury to health or the environment from exposure to chemical substances. It has been said that TSCA is the most powerful, wide-ranging environmental law in the world. Prior to its enactment, there had been extensive public discussion about the possible harmful effects to workers and the general public from the manufacture, processing, distribution, use, and disposal of chemicals. 

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