to be the same as assimilation efficiency of the experimental 

 animal in the bioassay used to determine a Carcinogenic 

 Potency Factor or RfD) 



6. Variation of exposure factors among individuals, such as: 



• Variation in fishery species composition of the diet 

 among individuals 



• Variation in food preparation methods and associated 

 changes in chemical composition and concentrations 

 due to cooking. 



Variance in estimates of carcinogenic potency or RfDs (#1 above) 

 account for one major uncertainty component in most risk assessments. 

 Chemical potencies are estimated only on an order-of-magnitude 

 basis, whereas analytical chemistry of tissues is relatively precise (on 

 the order of Jl20 percent). The choice of a low-dose extrapolation 

 model greatly influences estimates of the Carcinogenic Potency Factor 

 and calculated risks. This uncertainty contributed by the model is 

 substantial when predicting risks below 10' . For example, the 

 plausible-upper limit to lifetime cancer risk associated with 50 /<g/L 

 tetrachloroethene in drinking water ranges from about 10' for the 

 probit model to lO''^ for the Weibull model (Cothern et al. 1986). Model 

 uncertainty is important when considering absolute risk estimates (e.g., 

 Cothern et al. 1986), but less important for relative risk comparisons. 



Uncertainty analysis conducted by previous researchers illustrates the 

 variability of risk estimates and potency factors for a given extrapola- 

 tion model. For example, the coefficient of variation for the mean value 

 of potency generally ranged from 2 to 105 percent for each drinking 

 water contaminant studied by Crouch et al. (1983). This uncertainty 

 arose mainly from error associated with experimental bioassay data for 

 a single animal species. Among bioassay species, the potency of a given 

 chemical may vary only slightly or up to approximately 1,000-fold, 

 depending on the chemical in question (Clayson et al. 1983). Thus, the 

 uncertainty associated with extrapolating potency factors from 

 laboratory animals to humans may be much greater than the uncertain- 

 ty associated with animal bioassay techniques. By comparison, the 

 range of potencies among carcinogens covers 7-9 orders of magnitude 

 (Clayson et al. 1983; U.S. EPA 1985a). Relative risk comparisons 

 among chemicals can be made more confidently when the range of 

 potency factors is broad. Note that such comparisons should also 

 include consideration of the qualitative uncertainty (e.g., weight of 

 evidence) in assessing the specific health effects of chemicals, including 

 mode of action, latency period, and target organs. 



In conclusion, uncertainty ranges (e.g., 95 percent confidence inter- 

 vals) around estimates of mean risk may typically span at least several 

 orders of magnitude. The approach taken by U.S. EPA (1980b, 1985a, 

 1986a) and followed herein is to estimate a plausible-upper limit to risk. 

 In this way, it is unlikely that risk will be underestimated substantially. 

 Moreover, the plausible-upper-limit estimate serves as a consistent 

 basis for relative risk comparisons. However, the effects of compound- 

 ing conservative assumptions should be evaluated to provide perspec- 

 tive on risk assessment results. 



73 



