Toxicity Testing Strategies to Determine Needs and Priorities (1984) / Chapter Skim
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2. DESIGN OF THE PRIORITY-SETTING SYSTEM
2. DESIGN OF THE PRIORITY-SETTING SYSTEM
Pages 207-226
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From page 207... ...
Components of the system must also be described explicitly in terms of the number of toxic chemicals among the chemicals considered, the effectiveness of each procedure or toxicity test, and the resources required for each such procedure or test. The value-of-information concept is used to address the issue of which information is best to collect in each stage.
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From page 208... ...
The above goal also implies that toxicity testing and the gathering of information on human exposure should be considered jointly in assessing the potential public-health impact of a chemical. Because concern about a substance depends not only on its intrinsic toxicity, but also on the extent of human exposure to it, the gathering of information on the numbers of people exposed to various concentrations of the chemical may be just as important in setting its priority for testing as is determining its potential for toxicity.
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From page 209... ...
Some of the schemes reviewed by the Committee on Priority Mechanisms have been applied only to specific classes of chemicals (such as food additives or drugs) ; others have been applied only to chemicals on existing priority lists or to chemicals nominated by panels of experts (see Appendix A)
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From page 210... ...
Although the omission of such substances and mixtures can usually be understood on the grounds of convenience and practicality, it should be recognized that the classes of substances that are omitted include many that are both poorly characterized and potentially harmful. STRUCTURE OF THE SYSTEM The entire process of priority-setting and toxicity testing consists of a series of interconnected steps, each containing an informationgathering component and a decision-making component.
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From page 211... ...
FIGURE 1 Example of one stage or building block in process of investigation and control of toxic substances. Information-gathering activity here is toxicity test that produces useful data.
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From page 212... ...
A more complex type of multistage system is the decision tree, in which the screening criteria applied at each stage depend on the outcome of the previous stage. In most multistage systems, the first stage is a simple screen based on chemical class, use, or production volume; the second stage is based on criteria that reflect exposure; and the third and later stages are based on criteria that reflect toxicity or potential risks.
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From page 213... ...
The different degrees of concern can be thought of as ranges on a meter, with high readings generally warranting serious social concern and low ones suggesting that little or no concern is called for. The meter would register higher readings to the extent that there was an increase in any of the following: · Number of people exposed.
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From page 214... ...
Although there might be other reasons to test cigarette smoke further, an analysis based on the value of information would imply that the classification of high publichealth concern was good enough, and that further testing would not markedly improve it. Another study of the carcinogenicity of vinyl chloride at very low exposures might or might not be warranted, but it would probably have a lower priority than a lifetime bioassay on a chemical that was similar to vinyl chloride in structure, uses, and exposures and that was mutagenic in vitro, but had never been tested in a rodent bioassay.
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From page 215... ...
, there would be nine categories of hazard, each corresponding to a different pairing of exposure and toxicity. (Some might turn out to be equivalent to one another, e.g., high toxicity and low exposure, low toxicity and high exposure, and medium toxicity and medium exposure.)
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From page 216... ...
production or extraction manufacturing process transportation storage use environmental transformation bioaccumulation industrial discharge waste disposal environmental transport If all such information could be acquired, one could imagine dividing each dimension of exposure (route, amount, frequency, etc.) into ranges and then classifying all exposed people into groups defined by every combination of these ranges.
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From page 217... ...
Of the entire universe of chemicals, probably only a few substances are usually considered to be in the high exposure region, more are in the medium region, and most are in the low region. This distribution conforms with common perceptions about the number of toxic chemicals to which humans are exposed at high concentrations.
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From page 218... ...
are commonly used in testing for human health effects. In the best circumstances, toxicologists may be able to predict a particular activity of a chemical, ascribe a potential effect, identify a useful end point in an established animal model, elucidate the mechanism of the effect, and arrive at the conclusion that the chemical either will have no toxic effect in humans or will cause a measurable effect.
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From page 219... ...
Therefore, it is customary to depend on data from toxicity tests in animals, from which extrapolations are made to predict health effects in humans. The most useful data are those derived from an accepted animal model for a given chemically induced condition in humans, but adverse effects in animals not related to a known disease in humans are also of value.
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From page 221... ...
, and the scores are combined by a rule (often a weighted addition) to yield a single score that represents relative toxicity, relative exposure, or relative overall hazard.
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From page 222... ...
DESIGN FACTORS DESCRIBING THE PRIORITY-SETTING SYSTEM While choosing the elements of the priority-setting system, the designer should consider that the system must respond to the following external parameters: the nature of the chosen universe of chemicals, accuracy of selection stages or other components and accuracy of the toxicity testis) for which the system is selecting chemicals, and costs of the system components and toxicity tests.
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From page 223... ...
First, it is necessary to make some judgment about the relative importance of a false-negative and a false-positive for a given effect. This judgment is built into the design by the relative weights attached to the upper right and lower left corners of Figure 2.
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From page 224... ...
TABLE 2 Possible Results of Test Having Three Results: High, Medium, and Low Result of Test True Toxicity Low Medium High Low Correct False-negative Greatest false-negative Medium False-positive Correct Greater false-negative High Greatest Greater Correct false-positive false-positive 224
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From page 225... ...
. C and its subscripts indicate cell into which chemical is categorized and false and true classifications.
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From page 226... ...
are used in designing selection processes to ensure the selection of the most productive information-gathering activities per dollar spent. Cost data for toxicity tests are described in Stage 4 in Chapter 4.
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