Cancer risk assessment uncertainties

On the basis of the discussions and considerations presented in the earlier sections of this chapter on cancer risk assessment, the NAC/AEGL Committee has developed no AEGL values based on carcinogenicity. In view of the great uncertainty of the assumptions used in extrapolating from lifetime exposures to 8 h or less, the paucity of single-exposure inhalation data, the relatively... 

Stayner L, Bailer AJ, Smith R, et al. 1999. Sources of uncertainty in dose-response modeling of epidemiological data for cancer risk assessment. Arm N Y Acad Sci 895 212-222. 

Figure 4 Model uncertainty in cancer risk assessment.

Science policy issues and controversies underlie almost every aspect of cancer risk assessment. These policy issues are primarily a function of the scientific uncertainties inherent in risk assessment. As new scientific methods and data begin to fill in some of the data gaps and uncertainties in risk assessment, the role of policy will gradually recede, although there is no prospect of policy issues being mooted entirely in the foreseeable future. Moreover, the extent to which we substitute novel scientific data and models for preexisting policy inferences is itself an ongoing policy debate, as is the appropriate role of precaution and conservatism in risk assessment. 

By facilitating the simulation of the dose metrics for use in cancer dose-response analysis, the PBPK models address the uncertainty associated with interspecies, route-to-route, and high-dose to low-dose extrapolations (Andersen et al. 1993 Andersen and Krishnan 1994 Clewell et al. 2002a Clewell and Andersen 1987 Melnick and Kohn 2000). Since the first demonstration of the application of PBPK models in cancer risk assessment by Andersen and co-workers in 1987, there have been substantial efforts to evaluate the appropriate dose metrics and cancer risk associated with a number of other volatile organic chemicals using the PBPK modeling approach (Table 21.3). These risk assessments have been based on the PBPK model simulations of a variety of dose metrics that reflect the current state... 

Dourson ML, Eelter SP, Robinson D, Evolution of science-based uncertainty factors in non-cancer risk assessment, Regul. Toxicol. Pharm. 1996 24 108-120. 

An additional variable not dealt with completely in these risk analyses, is the expected type of tuoior. The tumors produced in the mouse were hemangioendotheliomas in the abdominal organs and tissues. Aniline residues passing through the human bladder are suspect as having the potential of producing more serious tumors at this site. This variable adds to the uncertainty of cancer risk assessment for human exposure based on laboratory animal data. 

There are many definitions of the word risk. It is a combination of uncertainty and damage a ratio of Itazards to safeguards a triplet combination of event, probability, and consequences or even a measure of economic loss or human injury in terms of both the incident likelihood and tlie magnitude of the loss or injuiy (AICliE, 1989). People face all kinds of risks eveiyday, some voluntarily and otliers involuntarily. Tlierefore, risk plays a very important role in today s world. Studies on cancer caused a turning point in tlie world of risk because it opened tlie eyes of risk scientists and healtli professionals to tlie world of risk assessments. 

Due to the various sources of uncertainties associated with both groups of input data (dose and effect) needed for risk assessment, at present it is only possible to give an upper limit for the pure Rn-d related cancer risk. 

To adjust for uncertainties in assessing potential cancer risks for short-term exposures under the multistage model, the 24-h exposure is divided by an adjustment factor of 6 (Crump and Howe 1984). 

In this paper I have tried to show that measurement of health benefits attributable to TSCA is not feasible. I hope that in doing so I have not belabored the obvious. For new chemicals and for most existing chemicals, prospective evaluation of health benefits to be achieved by various exposure controls will have to be based on extrapolation from microbial and animal data. However, while such extrapolation may be useful in a qualitative sense, quantitative risk assessment techniques involve considerable uncertainty, and in any case have not been developed for chronic effects other than cancer. 

Most scientists would hold that these unknowns and uncertainties in the regulatory risk-assessment model would tend to favor risk overestimation rather than underestimation or accurate prediction. While this view seems correct, it must be admitted that there is no epidemiological method available to test the hypothesis of an extra lifetime cancer risk of about 10 per 1000 000 from methylene chloride in drinking water. The same conclusion holds for most environmental carcinogens. It is also the case that more uncertainties attend the risk assessment process than we have indicated above. 

Gaylor, D.W., R.L. Kodell, J.J. Chen, and D. Krewski. 1999. A unified approach to risk assessment for cancer and noncancer endpoints based on benchmark doses and uncertainty/safety factors. Regul. Toxicol. Pharmacol. 29 151-157. 

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