Single chemicals exposures

When die hazard index exceeds miity, diere may be concern for potential health effects. While any single chemical with an exposure level greater than the toxicity value will cause die hazard index to e.xceed unity, die reader should note diat for multiple chemical exposures, die hazard index can also exceed unity even if no single chemical exposure exceeds its RfD. 

The approach described above is tailored to single chemical exposure assessments, although the general process could also be used for other types of hazards (e.g., biological hazards). Sometimes the focus of an exposure assessment will not be an assessment of human and ecological exposures to... 

Figure 2.8 Simulations of venous blood concentrations of toluene and ethylbenzene when maximal impact of inhibition (E = 0) (thick line) and maximal impact of induction (E = 1) (dotted line) are considered in rats exposed for a duration of 4 hours at 100 ppm. Experimental data are shown for these chemicals exposed alone and in mixtures of 2 to 10 VOCs, each indicated by a different symbol. The thin line represents the simulation of the single chemical exposure scenario. (Redrawn from Haddad et al. [2000c].)...

Component methods include those based on the assumption of response addition (e.g., addition of probabilistic cancer risks) or dose addition (e.g., relative potency factors (RPFs), hazard indexes (HI)). The advantages of component methods include an ability to utilize single chemical exposure and dose-response information to estimate a mixture risk and the flexibility to compare mixtures containing the same chemicals, but in different concentrations and proportions. 

For single chemical exposures, we know that most individuals are affected by very high concentrations. Individuals who are genetically predisposed and/or have been previously sensitized react to lower concentrations of a chemical. Effects at different concentration levels are, for the most part, known and predictable, enabling proper precautions to be taken. M... 

Our inability to defend ourselves against new chemicals and mixtures often results in epidemics of disease. For example, asthma, autism, infertility, and many cancers affect different parts of the body and seemingly have different etiologies. All, however, can be related to a combination of genetic predisposition and environmental exposure to chemicals. All are less prevalent where chemical exposures are lower, for example, in rural areas. All have known single chemical exposure causes and they can all be related to low level exposure to chemical mixtures. The toxic effects of chemical mixtures are explored in the chapters that follow. 

On-the-job exposures offer insight into the toxic effects of chemical mixtures. Though many health effects can be attributed to exposures to single chemicals, others cannot be accounted for by single chemical exposures and are clearly related to exposures to mixtures. This is particularly the case when at least one component of the mixture is a lipophile and at least one other component of the mixture is a hydrophile. The studies referenced in this chapter point out the need to consider mixture exposures when people present with symptoms, rather than dismiss their complaints as being of psychological origin. 

The continuing worldwide increase in respiratory disease corresponds to increases in the release of chemicals into the atmosphere. Respiratory irritation, sensitization, asthma, RADS, and lung cancer can be attributed to numerous single chemicals whose toxicological properties are, for the most part, well known. Many unexplained incidences of respiratory disease cannot be attributed to single chemical exposures, but have been shown to occur when exposures are to chemical mixtures that are composed of at least one lipophile and one hydrophile. The sources of such mixtures include diesel exhausts, tobacco smoke, carpet emissions, paint fumes, and cleaning products. Prevention of chemically induced respiratory diseases should include limiting exposures to these chemical mixtures. 

Xenobiotic exposure can adversely affect bones, joints, connective tissue, and muscles. Rheumatoid arthritis, osteoporosis, osteomalacia, systemic sclerosis, scleroderma, systemic lupus erythematosus, and spina bifida are musculoskeletal diseases that have been associated with toxic chemical exposures. Most of these associations, however, have been made to single chemical exposures and not to mixtures. This chapter cites the evidence on which those associations are based and discusses the available examples of mixtures that have been implicated. 

There are numerous mechanisms whereby one chemical may effect the activity of another, especially when all are present at biologically active doses. However, the results of such mixture studies must be discussed only in the context of the chemicals studied and of the experiments which were actually conducted. Often all that is reported is the simple conclusion that these studies prove that mixtures are different from single chemical exposures. Therefore, since mixtures of chemicals are found in our food, there must be a problem as toxicity studies have only been conducted with single chemicals. More chemicals must mean that even more toxicity may occur. This conclusion assumes that the toxic effects of all chemicals are additive, a hypothesis that actually is found rarely to hold in nature. The additional problem with this conclusion is that there is still no evidence of a real and significant health problem associated with eating food. 

Evaluations of occupational exposure to physical agents such as noise, radiation or heat, biological agents, and multiple chemical agents are similar to the process for single chemical substances but have some key differences. 

Exposure and development must be predictable and repeatable because multiple pieces of film may be used for a single plate exposure. The proper exposure source and the intensity of that source must be estabUshed. The imagesetter must be properly linearized to produce the desired precise halftone dots. This film must be handled under correct safelight conditions and machine-processed in chemical developers at the correct speed and temperature. 

MCS may result from a single massive exposure to one or more toxic substances or repeated exposure to low doses. On one hand, some people may become chemically sensitive following a toxic chemical spill at work or in their community or after being sprayed directly with pesticides. On the other, individuals may develop this condition from spending forty hours each week in a poorly ventilated building where they breathe a profusion of chemicals common to our modem way of life. 

The chances are generally not die same. Exposure depends on both die amount of clicinical exposure and die frequency of chemical exposure. Repealed exposure to low levels of a mix of chemicals may be linked to liealdi problems. However, a single incident at a higher level, if below a toxic direshold, may not be linked to liealdi problems. 

For some toxins it is possible to demonstrate an apparent improvement in functional response at levels of exposure which are below a threshold. This effect, which has been termed hormesis , is most effectively demonstrated in the consistently improved longevity of animals whose caloric intake is restricted rather than allowing them to feed ad lib (Tannenbaum, 1942). Clearly in this instance, the observed effects are the result of exposure to a complex mixture of chemicals whose metabolism determines the total amount of energy available to the organism. But it is also possible to show similar effects when single chemicals such as alcohol (Maclure, 1993), or caffeic acid (Lutz et al., 1997) are administered, as well as for more toxic chemicals such as arsenic (Pisciotto and Graziano, 1980) or even tetrachloro-p-dibenzodioxin (TCDD) ( Huff et al., 1994) when administered at very low doses. It is possible that there are toxins that effect a modest, reversible disruption in homeostasis which results in an over-compensation, and that this is the mechanism of the beneficial effect observed. These effects would not be observed in the animal bioassays since to show them it would be necessary to have at least three dose groups below the NOAEL. In addition, the strain of animal used would have to have a very low incidence of disease to show any effect. 

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