Cancer risk assessment quantitative

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. 

The fundamental question of risk assessment for potential human carcinogens requires definition of substances that exceed an evidentiary threshold. Once the scientific evidence establishes a substantial basis for conclusion of known or potential human cancer, it is then in order to determine a procedure for risk quantification. Quantitative risk assessments must always be read with the qualitative evidence of the likelihood of carcinogenicity. 

A different approach, called a quantitative risk assessment, is used for nonthreshold effects, such as cancer. Sophisticated statistical models are used to extrapolate the experimental animal data obtained at high doses to the low exposures predicted in humans. The linearized multistage (LMS) model is frequently... 

Hornung RW, Meinhardt TJ. 1987. Quantitative risk assessment of lung cancer in USA uranium miners. Health Phys 52 417-430. 

Fan AM and Howd R (2001) Quantitative risk assessment of non-genotoxic carcinogens. In Choy WN (ed.) Genetic Toxicology and Cancer Risk Assessment, pp. 299-320. New York Dekker. 

As there are no reports of adverse effects from consumption of excess thiamine from food and supplements (supplements of 50 mg/day are widely available without prescription), and the data are inadequate for a quantitative risk assessment, no UL has been defined for thiamine. However, as stimulators of transketolase enzyme synthesis such as thiamine support a high rate of nucleic acid ribose synthesis necessary for tumor cell survival, chemotherapy resistance, and proliferation, some concern has been expressed that thiamine supplementation of common food products may contribute to increased cancer rates in the Western world. There is, however, littie evidence to support this assumption. Rarely, individuals given high-dose intravenous thiamine in treatment of beriberi have developed anaphylaxis, the frequency being about 1 100,000. 

Velazquez, S. F., McGinnis, P. M., Vater, S. T., Stiteler, W. S., Knauf, L. A., and Schoeny, R. S. (1994). Combination of cancer data in quantitative risk assessments Case study using bromodichloromethane. Risk Anal 14, 285-292. 

Extrapolating Rodent Cancer Test Results to Humans. It is prudent to assume that if a chemical is a carcinogen in rats and mice at the maximum tolerated dose (MTD), it is also likely to be a carcinogen in humans the MTD. However, until we understand more about mechanisms, we cannot reliably predict risk to humans at low doses, often hundreds of thousands of times below the dose where an effect is observed in rodents. Thus, quantitative risk assessment is currently not scientifically possible (1.17,20). 

There are, of course, two extreme views of the validity of such quantitative risk assessment. On the one hand, it is held that there is no valid method for extrapolating cancer data in animals to arrive at risk assessments for humans. 

HEI (Health Effects Institute). 1999. Diesel Emissions and Lung Cancer Epidemiology and Quantitative Risk Assessment. Cambridge, MA Health Effects Institute. 

The chronic daily intake (CDI) estimated in the analysis of exposure, the second step of the risk assessment, is used to calculate the risks of both noncancer health effects and cancer. Risk calculations are also referred to as quantitative risk assessment, a term that is somewhat misleading because the word quantitative implies a high degree of accuracy, which is clearly not the case. In the first risk scenario described in Section 8.3, future residents drink arsenic-contaminated water from the aquifer beneath a former Superfund site. Their CDI by this pathway is estimated to be 0.0I6I mg/kg/day of arsenic. The oral reference dose (RfD) for arsenic is 3 x lO"" mg/kg/day, according to the EPA s Integrated Risk Information System (IRIS) (U.S. EPA 2009). The hazard index (HI) for noncancer health effects caused by this chemical of concern by this exposure pathway is calculated using Equation (8.3) ... 

Discussing the uncertainties involved in risk calculations is an important aspect of risk characterization. Quantitative risk assessments are fraught with uncertainty. Estimates of exposure (chronic daily intake) are probably accurate to roughly a factor of 10. Toxicity values—the reference dose for noncancer health effects and the slope factor for cancer risk—are also essentially order-of-magnitude estimates. As a result of these uncertainties, quantitative risk assessment gives a number that could be... 

The four steps of the risk-assessment process are hazard identification, analysis of exposure, analysis of effect, and risk characterization. In the hazard identification step, the risk assessor identifies chemicals of concern, environmental pathways of exposure, and populations and subpopulations at risk. The exposure analysis develops exposure scenarios and estimates the chronic daily intake of each chemical of concern. In the analysis of effect, the risk assessor combines the chronic daily intake calculated in the exposure analysis with toxicity data from animal studies (and/or human epidemiological studies, if available) to estimate the risk of toxic effects in exposed populations, whereby risks to public health are divided into two broad categories noncancer health effects and cancer. The final step of the risk-assessment process, risk characterization, is a narrative that marshals all the evidence of risk to public health, including quantitative risk assessments and qualitative evidence of risk. The risk assessor weighs all the evidence and uses professional judgment to draw conclusions about risks. 

In animal experiments exposures can be carefully controlled, and dose-response curves can be formally estimated. Extrapolating such information to the human situation is often done for regulatory purposes. There are several models for estimating a lifetime cancer risk in humans based on extrapolation from animal data. These models, however, are premised on empirically unverified assumptions that limit their usefulness for quantitative purposes. While quantitative cancer risk assessment is widely used, it is by no means universally accepted. Using different models, one can arrive at estimates of potential cancer incidence in humans that vary by several orders of magnitude for a given level of exposure. Such variations make it rather difficult to place confidence intervals around benefits estimations for regulatory purposes. Furthermore, low dose risk estimation methods have not been developed for chronic health effects other than cancer. The... 

Lipsett MJ, Carmelli D, Winship-Ball A, et al. 1982. Quantitative cancer risk assessment for occupational exposure to ethylene dibromide. Govt Reports Announcements Index (GRA I). Cincinnati, OH Robert A. Taft Labs. NTIS/PB83-184325... 

Cancer risk assessment is basically a two-step procedure, involving a qualitative assessment of how likely it is that a compound is a human carcinogen, and a quantitative assessment of the cancer risk that is likely to occur at given exposure levels and duration of exposure. 

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