Increased Lifetime Cancer Risk Research Articles

AN EVENT-BY-EVENT PROBABILISTIC METHODOLOGY FOR ASSESSING THE HEALTH RISKS OF PERSISTENT CHEMICALS IN FISH: A CASE STUDY AT THE PALOS VERDES SHELF

A human health risk assessment of recreational anglers who consume fish from the Palos Verdes Shelf was conducted. The uptake of DDT, DDE, and DDD (collectively total DDT or tDDT) and polychlorinated biphenyls (PCBs) due to fish ingestion was characterized using Monte Carlo techniques. This analysis relied upon 176 probability density functions developed from over 300,000 individual pieces of information to represent 17 different exposure factors that influence the human uptake of persistent organic chemicals in fish. The carcinogenic and noncarcinogenic risks were estimated using a microexposure event modeling approach that estimates exposure on an event-by-event basis. This evaluation relied upon several large studies that provided site-specific data on angler behavior and concentratioins of chemicals in 13 fish species. Our results indicate that the median theoretical increased lifetime cancer risk associated with estimated exposure to tDDT and PCBs was 5 x 10(-8) for anglers who fish on commercial passenger fishing vessels (CPFVs) and who catch and eat fish from the Palos Verdes Shelf. The mean risk for these anglers was 2 x 10(-7), and the 95th percentile risk was 8 x 10(-7). At the 9.5th percentile, the hazard quotients for anglers were less than 1, indicating that noncancer effects are unlikely. These results are in contrast with prior risk assessments of this site that suggested that consumption of white croaker alone posed a cancer risk of 2 x 10(-3) and a hazard quotient of 32. Our results were validated by their agreement with several independent local studies regarding fishing and consumption practices. This assessment indicates that the levels of tDDT and PCB in fish at the Palos Verdes Shelf do not pose a significant risk to human health among recreational anglers. Based on the size of the local angler population, no cases of cancer would be expected to result from eating Palos Verdes Shelf fish. The methodology used here should be applicable to characterizing the risks to those who ingest fish from the waterways of most industrialized nations.

Risk Assessment of Inhaled Chloroform Based on Its Mode of Action

The development of scientifically sound risk assessments based on mechanistic data will enable society to better allocate scarce resources. Inadequate risk assessments may result in potentially dangerous levels of hazardous chemicals, whereas overly conservative estimates can result in unnecessary loss of products or industries and waste limited resources. Risk models are used to extrapolate from high-dose rodent studies to estimate potential effects in humans at low environmental exposures and determine a virtually safe dose (VSD). When information to the contrary is not available, the linearized multistage (LMS) model, a conservative model that assumes some risk of cancer at any dose, is traditionally employed. In the case of airborne chloroform, the dose at which an increased lifetime cancer risk of 10(-6) could be calculated was chosen as the target VSD. Applying the LMS model to the mouse liver tumor data from a corn-oil gavage bioassay yields a VSD of 0.000008 ppm chloroform in the air. The weight of evidence indicates that chloroform is not directly mutagenic but, rather, acts through a nongenotoxic-cytotoxic mode of action. In this case, tumor formation results from events secondary to induced cytolethality and regenerative cell proliferation. Toxicity is not observed in rodents when chloroform is not converted to toxic metabolites at a rate sufficient to kill cells. Thus, tumors would not be anticipated at doses that do not induce cytolethality, contrary to the predictions of the LMS model. Inhalation studies in rodents show no cytolethality or regenerative cell proliferation in mouse liver at a chloroform concentration of 10 ppm as the no observed effect level (NOEL) or below. Using that NOEL and a safety factor approach, one can develop a VSD of 0.01 ppm. Integrating these data into the risk assessment process will yield risk estimates that are appropriate to the route of administration and consistent with the mode of action.