cinogens (U.S. EPA 1980b, 1986a; U.S. Office of Science and Tech- 

 nology Policy 1985) implies a finite risk of cancer even at very low doses 

 of the carcinogen. For noncarcinogenic effects, there is usually a 

 threshold dose (i.e., a dose below which no adverse biological effects 

 are observed in the animal bioassay). The threshold dose is termed the 

 No-Observed-Adverse-Effect-Level (NOAEL), as shown in Figure 2. 

 Note that a nonzero mean response may be a NOAEL if that mean 

 response is not significantly different from zero as determined by a 

 statistical test. The Lowest-Observed-Adverse-Effect-Level 

 (LOAEL) is the lowest concentration that results in a statistically 

 significant health effect in the test population. 



A measure of toxicological potency is derived from an empirical 

 dose-response relationship for the chemical of interest. Toxicological 

 potency indices for two broad categories of toxicants are defined as 

 follows: 



• Carcinogens are individually characterized by a Carcinogenic 

 Potency Factor, a measure of the cancer-causing potential of a 

 substance estimated as the upper 95 percent confidence limit 

 of the slope of a straight line calculated by the linearized 

 multistage procedure or another appropriate model 



• Noncarcinogens are individually characterized by an RfD, an 

 estimate of the daily exposure to the human population (includ- 

 ing sensitive subpopulations) that is unlikely to produce an 

 appreciable risk of adverse health effects during a lifetime. 



Carcinogenic Potency Factors are also referred to as Slope Factors. 

 The RfD is conceptually similar to an Acceptable Daily Intake (U.S. 

 EPA 1987a). 



The data set used to define toxicological indices is determined by the 

 quality of available data, its relevance to modes of human exposure, 

 the similarity of the species to humans, and other technical factors. 

 Adequate data from clinical or epidemiological studies of humans are 

 preferred over animal data. If adequate human data are not available, 

 a data set for the animal species most similar to humans or for the most 

 sensitive species is used in the dose-response assessment. Data are 

 evaluated by EPA to ensure high quality (e.g., U.S. EPA 1980b, 1985a). 



The main source of dose-response data for deriving Carcinogenic 

 Potency Factors and RfDs is Ufetime cancer bioassays performed on 

 rats or mice. Because most of these experiments are designed to be 

 cost-effective, doses in bioassays may be orders of magnitude above 

 those encountered in the human environment. High doses are used in 

 laboratory bioassays for several reasons: 1) to reduce the time re- 

 quired to produce a response and thus overcome problems related to 

 latency period (i.e., length of time between exposure and appearance 

 of health effects), 2) to obtain sufficient statistical power to detect 

 health effects, and 3) to decrease the absolute number of animals 

 required and thereby reduce costs. Doses in animal bioassays for oral 

 uptake of contaminants are usually the administered (ingested) dose, 

 not the absorbed dose (i.e., uptake across the lining of the gastro- 

 intestinal system). 



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