Exposure, chemical distribution

Tier 2 PRA process involved developing environmental exposure data and chronic toxicity data distributions for individual POPs. The mean concentrations of POPs in local marine water measured at various locations were used as exposure data in the construction of the exposure distribution. The chronic toxicity data distribution was established based on published international acute toxicity data (LC50, EC50) on a variety of aquatic organisms tested in many jurisdictions, drawn primarily from the USEPA ECOTOX database (2002) (available at http //www.epa.gov/ ecotox). If the upper 5th centile of the measured chemical exposure data distribution did not exceed the lower 5th centile of its estimated chronic toxicity distribution, the potential ecological risk posed by the chemical was judged to be tolerable (Hall and Giddings, 2000). 

The health impacts of chemicals are significant, though difficult to quantify. Some estimates are available (WHO 2002) indicating that about 5% of the global burden of disease can be attributed to environmental chemicals exposures. The distribution of effects across the globe is the result of the combined effect of the volume of chemicals use and the effectiveness of chemical safety measures. In the countries of the OECD (Organisation for Economic Co-operation and Development) in general... 

This chapter provides an overview of factors affecting dermal absorption. Factors influencing absorption are among others related to the skin (e.g. anatomical site, difference between species, metabolism, etc.) and the exposure conditions (e.g. area dose, vehicle, occlusion and exposure duration). In order to provide relevant information for the risk assessment of pesticides, dermal absorption studies should take these aspects into account. With respect to the methods being used nowadays for the assessment of dermal absorption, it is important to realize that neither in vitro nor in vivo animal studies have been formally validated. Available data from various in vitro studies, however, indicate that the use of the total absorbed dose (i.e. the amount of test substance in the receptor medium plus amount in the skin) could be used in a quantitative manner in risk assessment. Tape stripping of the skin can be adequate to give a good indication of test chemical distribution, and hence its immediate bioavailability. 

In repeated-dose exposures, chemicals have a chance to accumulate in the body. The level a chemical reaches in the body depends on how large and frequent the doses are as well as on the chemical s disposition in the body, i.e., its bioavailability, volume of distribution, and rate of elimination. The blood level of a chemical at any point in time in effect reflects a steady state between the amount of chemical that enters the body and the amount that leaves. The principle of mass balance (Section 2.8) can be used to estimate body burden ... 

Olfactory receptors have been a subject of great interest (9). Much that has been postulated was done by analogy to the sense of sight in which there are a limited number of receptor types and, as a consequence, only three primary colors. Thus attempts have been made to recognize primary odors that can combine to produce all of the odors that can be perceived. Evidence for this includes rough correlations of odors with chemical stmctural types and the existence in some individuals having specific anosmias. Cross-adaptation studies, in which exposure to one odorant temporarily reduces the perception of a chemically related one, also fit into this hypothetical framework. Implicit in this theory is the idea that there is a small number of well-defined odor receptors, so that eventually the shape and charge distribution of a specific receptor can be learned and the kinds of molecular stmctures for a specified odor can be deduced. 

Toxic Substances Control Act. EPA regulates the manufacture, use, and exposure to ha2ardous or toxic chemicals under a number of laws. Eor the chemical industry, the law of prime concern is the Toxic Substance Control Act (TSCA) (10), which was passed by the U.S. Congress in 1976. The two main goals of TSCA are acquisition of sufficient information to identify and evaluate potential ha2ards from chemical substances, and regulation of the production, use, distribution, and disposal of these substances. 

As part of TSCA, EPA can require the testing of any chemical if there is the possibiUty of an unreasonable risk to health or environment or if there is significant human or environmental exposure. If the substance poses an unreasonable risk, EPA can prohibit the manufacture, processing, or distribution of the substance limit the amount of the substance that can be manufactured, processed, or distributed prohibit a particular use for the substance limit the concentration of the substance during manufacture, processing, or distribution regulate disposal methods for the substance and require manufacturers to maintain records of process and to conduct tests to assure compliance with EPA rules. 

The Toxic Substances Control Act (TSCA) was enacted in 1976 to identify and control toxic chemical ha2ards to human health and the environment. One of the main provisions of TSCA was to estabUsh and maintain an inventory of all chemicals in commerce in the United States for the purpose of regulating any of the chemicals that might pose an unreasonable risk to human health or the environment. An initial inventory of chemicals was estabhshed by requiring companies to report to the United States Environmental Protection Agency (USEPA) all substances that were imported, manufactured, processed, distributed, or disposed of in the United States. Over 50,000 chemical substances were reported. PoUowing this initial inventory, introduction of all new chemical substances requires a Premanufacturing Notification (PMN) process. To be included in the PMN are the identity of the new chemical, the estimated first year and maximum production volume, manufacture and process information, a description of proposed use, potential release to the environment, possible human exposure to the new substance, and any health or environmental test data available at the time of submission. In the 10 years that TSCA has been in effect, the USEPA has received over 10,000 PMNs and up to 10% of the submissions each year are for dyes (382)... 

CASRAM predicts discharge fractions, flash-entrainment quantities, and liquid pool evaporation rates used as input to the model s dispersion algorithm to estimate chemical hazard population exposure zones. The output of CASRAM is a deterministic estimate of the hazard zone (to estimate an associated population health risk value) or the probability distributions of hazard-zones (which is used to estimate an associated distribution population health risk). 

In general, it is easier to use models such as these to predict the distribution of chemicals (i.e., relationship between exposure and tissue concentration) than it is to predict their toxic action. The relationship between tissue concentration and toxicity is not straightforward for a diverse group of compounds, and depends on their mode of action. Even with distribution models, however, the picture can be complicated by species differences in metabolism, as in the case of models for bioconcentration and bioaccumulation (see Chapter 4). Rapid metabolism can lead to lower tissue concentrations than would be predicted from a simple model based on values. Thus, such models need to be used with caution when dealing with different species. 

Plant uptake is one of several routes by which an organic contaminant can enter man s food chain. The amount of uptake depends on plant species, concentration, depth of placement, soil type, temperature, moisture, and many other parameters. Translocation of the absorbed material into various plant parts will determine the degree of man s exposure—i.e., whether the material moves to an edible portion of the plant. Past experience with nonpolar chlorinated pesticides suggested optimal uptake conditions are achieved when the chemical is placed in a soil with low adsorptive capacity e.g., a sand), evenly distributed throughout the soil profile, and with oil producing plants. Plant experiments were conducted with one set of parameters that would be optimal for uptake and translocation. The uptake of two dioxins and one phenol (2,4-dichlorophenol (DCP)) from one soil was measured in soybean and oats (7). The application rates were DCP = 0.07 ppm, DCDD 0.10 ppm, and TCDD = 0.06 ppm. The specific activity of the com-... 

Respiratory Effects. One study suggested increased respiratory disorders (asthma, bronchitis, pneumonia) in children with chronic exposure to a solvent-contaminated water supply (Byers et al. 1988). Two municipal wells in eastern Woburn, Massachusetts, were found to contain several solvents including trichloroethylene (267 ppb) and tetrachloroethylene (21 ppb). The increased susceptibility to infection may be secondary to effects on the immune system. Accurate chemical-specific exposure levels for individuals could not be determined because the water distribution system was designed to use water from different wells at different rates and times. Other limitations of this study are described in Section 2.2.2.8. 

Production, Import/Export, Use, Release, and Disposal. Humans are at risk of exposure to trichloroethylene because of its widespread use and distribution in the environment. Production, import, and use of the chemical are known to be relatively high, but recent quantitative data were not available (HSDB 1994). Trichloroethylene is released to the atmosphere mainly through its use in vapor degreasing operations (EPA 1985e). Landfills can be a concentrated source of trichloroethylene on a local scale. It is also released to surface water and land in sewage sludges and industrial liquid or solid waste. Trichloroethylene is... 

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