Estimating cancer risk from outdoor concentrations of hazardous air pollutants in 1990.

A public health concern regarding hazardous air pollutants (HAPs) is their potential to cause cancer. It has been difficult to assess potential cancer risks from HAPs, due primarily to lack of ambient concentration data for the general population. The Environmental Protection Agency's Cumulative Exposure Project modeled 1990 outdoor concentrations of HAPs across the United States, which were combined with inhalation unit risk estimates to estimate the potential increase in excess cancer risk for individual carcinogenic HAPs. These were summed to provide an estimate of cancer risk from multiple HAPs. The analysis estimates a median excess cancer risk of 18 lifetime cancer cases per 100,000 people for all HAP concentrations. About 75% of estimated cancer risk was attributable to exposure to polycyclic organic matter, 1,3-butadiene, formaldehyde, benzene, and chromium. Consideration of some specific uncertainties, including underestimation of ambient concentrations, combining upper 95% confidence bound potency estimates, and changes to potency estimates, found that cancer risk may be underestimated by 15% or overestimated by 40-50%. Other unanalyzed uncertainties could make these under- or overestimates larger. This analysis used 1990 estimates of concentrations and can be used to track progress toward reducing cancer risk to the general population.

Assessing the cancer risk from environmental PCBs.

A new approach to assessing the cancer risk from environmental polychlorinated biphenyls (PCBs) considers both toxicity and environmental processes to make distinctions among environmental mixtures. New toxicity information from a 1996 cancer study of four commercial mixtures strengthens the case that all PCB mixtures can cause cancer, although different mixtures have different potencies. Environmental processes alter PCB mixtures through partitioning, chemical transformation, and preferential bioaccumulation; these processes can increase or decrease toxicity considerably. Bioaccumulated PCBs are of greatest concern because they appear to be more toxic than commercial PCBs and more persistent in the body. The new approach uses toxicity studies of commercial mixtures to develop a range of cancer potency estimates and then considers the effect of environmental processes to choose appropriate values for representative classes of environmental mixtures. Guidance is given for assessing risks from different exposure pathways, less-than-lifetime and early-life exposures, and mixtures containing dioxinlike compounds.

Plausible upper bounds: are their sums plausible?

Quantitative cancer risk assessments are typically expressed as plausible upper bounds rather than estimates of central tendency. In analyses involving several carcinogens, these upper bounds are often summed to estimate overall risk. This begs the question of whether a sum of upper bounds is itself a plausible estimate of overall risk. This question can be asked in two ways: whether the sum yields an improbable estimate of overall risk (that is, is it only remotely possible for the true sum of risks to match the sum of upper bounds), or whether the sum gives a misleading estimate (that is, is the true sum of risks likely to be very different from the sum of upper bounds). Analysis of four case studies shows that as the number of risk estimates increases, their sum becomes increasingly improbable, but not misleading. Though the overall risk depends on the independence, additivity, and number of risk estimates, as well as the shapes of the underlying risk distributions, sums of upper bounds provide useful information about the overall risk and can be adjusted downward to give a more plausible [perhaps probable] upper bound, or even a central estimate of overall risk.

Trichloroethylene health risk assessment: a new and improved process.

Trichloroethylene (TCE), an environmental contaminant of National concern, is the focus of a new health risk assessment process incorporating the Proposed Cancer Risk Assessment Guidelines. This paper describes not only how TCE became an environmental problem for the Air Force, but also details the new Risk Assessment process envisioned by the Environmental Protection Agency's (EPA) National Center for Environmental Assessment (NCEA). Insights on epidemiological evaluations, both past and future, and their impact on the cancer classification of TCE are discussed. Examples of how physiologically based pharmacokinetics and dose-response characterization described in the new Cancer Guidelines are applied to TCE are provided. In addition, a variety of modeling techniques are discussed for the development of reference doses (oral exposure) and reference concentrations (inhalation exposures) for TCE. Finally, the role of risk communication is included. This new process provides an example of how interagency (EPA, Department of Defense. Department of Energy) and extramural (industry, academia) partnerships can provide greater gains to the nation, as a whole, than any of the parts on their own.

Quantitative cancer assessment for vinyl chloride: indications of early-life sensitivity.

Complementary sources of information are analyzed to characterize the early-life cancer risk from inhaling vinyl chloride. A study of partial-lifetime exposures suggests that the lifetime cancer risk depends on age at exposure, with higher lifetime risks attributable to exposures at younger ages. Studies of newborn animal exposures further demonstrate that a brief exposure in newborns can, by the end of life, induce a higher incidence of tumors compared to long-term exposure occurring later in life, including tumor types not induced by exposure later in life. An empirical, quantitative approach is used to model early-life sensitivity to inhaled vinyl chloride, supplementing conventional approaches for estimating the increased cancer risk from lifetime exposure. A single estimate is not presumed to apply to the entire population; instead, the new approach makes distinctions about the cancer risks for different population segments. This assessment shows one way such information might be analyzed, presented, and used to assess actual exposure situations.

A case study of cancer data set combinations for PCBs.

Results of several animal bioassays have demonstrated the carcinogenic potential of polychlorinated biphenyl (PCB) mixtures. Although PCBs are no longer manufactured, cancer risk assessment for PCBs remains an important issue because of continued potential human exposure from many sources. The existing cancer risk estimate for PCBs used by the U.S. EPA is based on liver tumors observed in female Sprague-Dawley rats in a lifetime bioassay. Liver cancer has been observed in other long-term bioassays as well. In this case study, experimental designs and biological characteristics of the data from these studies were evaluated to determine whether a combination of the data sets is scientifically reasonable. A statistical analysis of the data sets based on likelihood ratio theory was used to assess the compatibility of individual data sets to a common multistage dose-response model. The results from these biological and statistical assessments suggest that at least two data sets could be combined to derive a quantitative risk estimate for PCBs. Increased confidence in the quantitative estimate would result from such combination because more data are being used to assess the dose-response relationship.