Acceptable lifetime cancer risk

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... 

The outcome of low-dose extrapolation is the resulting lifetime cancer risk associated with estimated exposure for a particular population. A wide range of models have been developed for low-dose extrapolation of animal data to calculate a tolerable intake for an acceptable risk, often set at one extra cancer per million exposed persons (see Section 6.2.4 for acceptable risk). 

There are no regulations, neither nationally nor internationally, governing acceptable/tolerable lifetime cancer risks as this decision is a policy issue. The acceptable/tolerable lifetime cancer risk may therefore vary from one authority to another and might be dependent on the target population as well as on policy issues such as social, economic, and political factors. As an administrative practice, an acceptable/tolerable lifetime cancer risk has often been set as 10 , i.e., at one additional cancer case per million exposed persons. 

The term acceptable is used to describe excess lifetime cancer risks in the range of about 10 4 to 10 6, the particular value depending on the exposure situation, or intakes of noncarcinogens less than EPA s reference doses (RfDs). 

The term unacceptable is used to describe lifetime cancer risks or intakes of noncarcinogens greater than acceptable levels. 

Okrent and Xing (1993) estimated the lifetime cancer risk to a future resident at a hazardous waste disposal site after loss of institutional control. The assumed exposure pathways involve consumption of contaminated fruits and vegetables, ingestion of contaminated soil, and dermal absorption. The slope factors for each chemical that induces stochastic effects were obtained from the IRIS (1988) database and, thus, represent upper bounds (UCLs). The exposure duration was assumed to be 70 y. Based on these assumptions, the estimated lifetime cancer risk was 0.3, due almost entirely to arsenic. If the risk were reduced by a factor of 10, based on the assumption that UCLs of slope factors for chemicals that induce stochastic effects should be reduced by this amount in evaluating waste for classification as low-hazard (see Section 7.1.7.1), the estimated risk would be reduced to 0.03. Either of these results is greater than the assumed limit on acceptable risk of 10 3 (see Table 7.1). Thus, based on this analysis, the waste would be classified as high-hazard in the absence of perpetual institutional control to preclude permanent occupancy of a disposal site. 

Chemical USEPA Cancer Classification21 Dietary Inhalation Total Excess Lifetime Cancer Risk Acceptable Range of Excess Lifetime Cancer Risk (USEPA)... 

Chemical USEPA Cancer Classification15 LADD (total, mg kg-1 bw d 1)d Slope factor6 Excess lifetime cancer risk Acceptable range of excess lifetime cancer risk (USEPA) ... 

Risk characterization includes a comparison between toxicity values and/or exposure criteria and exposure (dose or media concentration) to determine whether the exposure is acceptable. US EPA developed a formalized system that is commonly used to determine whether chemicals are likely to present an unacceptable risk based on current and likely future use of the property. The estimated dose is used to calculate an additional lifetime cancer risk for each chemical regulated as a carcinogen. Typically, a total site risk (sum of the risk associated with all carcinogens identified at the site) is presented. Acceptable risk is defined by the agency, in the appropriate laws, or by regulations that govern the site. Acceptable risk is a function of policy or law but is supposed to be rooted in science. 

Many chemical risks such as those of chloroform in drinking water, are calculated, not measured - that is, they are based not only on scientific data, but also on various sets of assumptions and extrapolation models that, while scientifically plausible (they fall within the bounds of acceptable biological theory), have not been subjected to empirical study and verification. Indeed, the results of most risk assessments - whether expressed as an estimate of extra cancer risk or an ADI - are scientific hypotheses that are not generally testable with any practicable epidemiological method. There is, for example, no practical means to test whether chloroform residues in chlorinated drinking water increase lifetime cancer risk in humans by 8 in 1000000, as hypothesized above. The tools of epidemiology are enormously strained, indeed, when called upon to detect the relatively low risks associated with most environmental chemicals. Without such a test, these risks remain unverified. 

For known or suspected carcinogens, acceptable exposure levels are generally concentration levels that represent an excess upper bound lifetime cancer risk to an individual of between 10 and 10 using information on the relationship between dose and response. The 10 risk level shall be used as the point of departure for determining remediation goals. 

The recommended dose limits for the public define limits on the probability of stochastic responses that are regarded as necessary for protection of public health. Doses above the limits are regarded as intolerable and normally must be reduced regardless of cost or other circumstances, except in the case of accidents or emergencies (see Section 3.3.1). For continuous exposure over a 70 y lifetime, and assuming a nominal probability coefficient for fatal cancers (i.e., the probability of a fatal cancer per unit effective dose) of 5 X 10 2 Sv 1 (ICRP, 1991 NCRP, 1993a), the dose limit for continuous exposure corresponds to an estimated lifetime fatal cancer risk of about 4 X 10 3. However, meeting the dose limits is not sufficient to ensure that routine exposures of the public to man-made sources would be acceptable. 

Establishing an acceptable risk or dose. There also are a number of precedents for establishing an acceptable (barely tolerable) risk or dose of substances that cause stochastic responses for the purpose of classifying waste as low-hazard or high-hazard. For radionuclides, the annual dose limit for the public of 1 mSv currently recommended by ICRP (1991) and NCRP (1993a) and contained in current radiation protection standards (DOE, 1990 NRC, 1991) could be applied to hypothetical inadvertent intruders at licensed near-surface disposal facilities for low-hazard waste. This dose corresponds to an estimated lifetime fatal cancer risk of about 4 X 10 3. Alternatively, the limits on concentrations of radionuclides in radioactive waste that is generally acceptable for near-surface disposal,... 

Implementation of emergency-response procedures based on theoretical excess risk values of 10 to 10 may be problematical. For example, if such values were used, they would be based on an anticipated increased cancer risk of 10 to 10 a policy consistent with EPA s acceptable cancer risk for lifetime exposures to known or suspect human carcinogens. However, the public health and safety risks associated with evacuation and other response measures might pose greater risks of injury or perhaps death. Thus, setting AEGL values based on uncertain theoretical cancer risk estimates might lead to response measures that increase actual or total risk for the exposed population. 

A5.2.2.9 The competent authority will need to establish what level of risk is acceptable to implement such an approach to consumer product labelling for chronic effects. For example, CPSC recommends labelling for a cancer hazard if the lifetime excess risk exceeds one-in-a-million from exposure during reasonably foreseeable handling and use. ... 

This question of whether it is scientifically valid to derive the lifetime control limit by using threshold or non-threshold models defines what cleanup levels are proposed for a site. The action level proposed by CDC for residential soil in Missouri is 1 ppb, based on a series of exposure assumptions and on virtually safe doses for 10"° cancer risk of 0.0276 pg/kg/day (U). If one assumes a different threshold - based model, as did Dutch, Swiss, German, and Canadian workers (9), one obtains maximum allowable daily intake of 1-10 pg/kg/day. If one uses the same exposure calculations as CDC, one could then accept 4-40 ppb in residential soil according to these allowable daily intakes. CDC and ERA have allowed 7 ppb as acceptable residual concentrations at an industrial site in New Jersey (IJ). At Seveso, cleanup levels were set at 45 ppt for nonagricultural soil and 7 ppt for agricultural soil... 

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