Cancer risk assessment unit

Application of cancer risk assessment values in the context of soil contamination is conducted in the United States under the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) of 1980, also known as the Superfund program. This law was enacted to address abandoned hazardous waste sites through development of a mechanism to provide funding and a process to rate the hazard of... 

Generally, the slope factor is a plausible upper bound estimate of the probability of a response per unit intake of a ehemieal over a lifetime. The slope factor is used in risk assessments to estimate an upper-bound lifetime probability of an individual developing cancer as a result of e.xposure to a particular level of a potential carcinogen. Slope factors should always be accompanied by the weight-of-evidence classification to indicate the strength of the evidence that the agent is a human carcinogen. Calculational details are presented below. 

Stern FB, Murthy LI, Beaumont JJ, et al Notification and risk assessment for bladder cancer of a cohort exposed to aromatic amines. III. Mortality among workers exposed to aromatic amines in the last 3-naphthylamine manufacturing facility in the United States. Occup Med27-.495-500, 1985... 

Estimates of Probability Coefficients for Carcinogens. The nominal probabilities of a stochastic response (primarily cancers) per unit dose used in risk assessments, which are referred to in this Report as probability coefficients, normally differ for radionuclides and chemical carcinogens in regard to the degree of conservatism incorporated in the assumed values and the number of organs or tissues at risk that are taken into account. 

The risk models described herein for carcinogens are not yet much used outside the United States. Carcinogens tend either simply to be banned, where it is possible to do so, or are treated the way non-carcinogens are treated in the United States. The discussion of risk assessment as applied to non-cancer forms of toxicity is thus applicable to carcinogens in countries outside the U.S.A. 

In the United States, the ERA is the lead agency on major waste sites, but there are thousands of smaller sites across the United States, for which states often take the lead. Because it is not possible to do a comprehensive cancer and noncancer risk assessment for each site (abandoned gas stations with petroleum hydrocarbon in the soil, for instance), the risk assessment process has been simplified with predefined cleanup standards for most common contaminants. These are often called Rreliminary Remediation Goals (RRGs) (ERA 2007). These may be modified by individual states to meet their own exposure or risk standards (CleanupLevels 2008). 

The assessment of liver cancer risks associated with human exposure to trichloroethylene (TCE) was initially conducted by Fisher and Allen (1993) using a PBPK-modeling approach. The use of the amount of TCE metabolized per day as dose metric used in the linearized multistage model led to lOppb in air and 7 ag/L in water as acceptable concentrations—that is, environmental levels corresponding to a population cancer risk of 1 in 10 (Fisher and Allen 1993). Corresponding values based on circulating levels of the metabolite, trichloroacetic acid, were 10 times and twice lower than those based on the amount of TCE metabolized per unit time, whereas the acceptable TCE concentration in air as defined by the EPA at the time was 90 times lower. A number of authors subsequently investigated the dose metrics and cancer risks associated with TCE [e.g., Bois (2000), CleweU and Andersen... 

For example, the Ontario risk assessment uses a no observable effect level (NOEL) of 0.001 ug/kg/day (6.73) and a safety factor of 100 to obtain a maximum allowable dally intake of 1 X 10" 1 g/kg/day (= 10 pg/kg/day) for humans (74). In contrast, EPA has used a value of 6.4 X 10" 5 g/kg/day which suggests cancer risks that are 1670 fold higher. The United States Food and Drug Administration (FDA) has, on the other hand, accepted risks associated with the ingestion of up to 13 pg/kg/day. (Table IX). 

As the toxicities (carcinogenicity and mutagencity) of individual PAHs differ considerably, toxicity assessments of PAHs are complex. A number of approaches have been developed for evaluating the potencies of the various PAHs with regard to the possible inhalation cancer risk to humans (lARC, 1983). One approach is to calculate the inhalation unit risk for excess lung cancer over the risk posed by BaP for each of its copollutant carcinogenic PAH in the polluted ambient air divided the particular PAH s risk by the risk... 

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