Risk-specific dose, carcinogens

The unit risk is defined as the upper bound additional lifetime cancer risk associated with exposure to either 1 pg 1 in water or 1 pg m in air. The dose or exposure concentration associated with a given risk can also be calculated by rearranging terms in the slope factor equation shown above to solve for the dose term. The result is termed the risk specific dose (or concentration). The risk specific dose is often used as the basis for the exposure criteria for carcinogens. 

The health assessment chapters of these documents contain the available dose-response data from animal experiments and human epidemiology studies for the chemical or class of chemicals of concern. By assessing the risks associated with various doses, acceptable daily intakes (ADIs - for systemic toxicants) or risk-specific doses (for carcinogens) were derived. These levels were divided by appropriate exposure assumptions (e.g., estimated average water consumption) to derive a criterion. 

With regard to carcinogenicity, a weight-of-the-evidence evaluation suggests that dioxin and related compounds (CDDs, CDFs, and dioxin-like PCBs) are likely to present a cancer hazard to humans [157]. While major uncertainties remain, efforts of this reassessment to bring more data into the evaluation of cancer potency have resulted in a risk-specific dose estimate (1 x 10 risk or one additional cancer in one million exposed) of approximately 0.01 pg TEQ/kg body weight/day. This risk-specific dose estimate represents a plausible upper bound on risk based on the evaluation of animal and human data. "True" risks are not likely to exceed this value, may be less, and may even be zero for some members of the population. 

A mutated cell may reproduce and begin the formation of a carcinogenic mass (tumor), and mutations may occur after acute or chronic exposure. The specific relationship between acute or chronic exposure rate and cancer risk is hotly debated, although current U.S. regulations conservatively adopted the linear no threshold (LNT) model. This model states that risk is linearly proportional to the total dose even at the smallest possible dose levels (risk is associated with all levels of dose no matter how small). An alternate model theorizes that no measurable adverse health effects appear below doses of about 10 to 25 rem (0.1 to 0.25 Sv). Data supporting both models are limited and, to be conservative, levels of exposure should be kept as low as reasonably achievable (ALARA). Victim and emergency responder doses and dose rate may not be easily controlled in the event of a terrorist attack. However, methods to achieve ALARA exposures are described in Chapters 4 and 5. 

Assessment of the carcinogenic risk to humans from a review of animal data is complicated by the results of pharmacokinetic studies that have associated methylene chloride carcinogenicity with a specific metabolic pathway. This glutathione S-mediated pathway appears to proceed slowly in humans compared with mice and only at high exposure doses. Therefore, extrapolation from high dose to low dose and between species may not provide accurate risk assessment of human exposure. 

The oral reference dose (Oral RfD) is an estimate of the daily exposure of a person to a contaminant that is likely to be without appreciable risk of a deleterious non-carcinogenic effect during a lifetime (USEPA http //www.epa.gov/iris/). Oral RfD values for POP concentrations in seafood types are presented in Table 16.5, together with the daily intake of POPs from seafood consumed in Singapore. Daily intakes of POPs from seafood are below the oral RfD. The cancer benchmark concentration (Dougherty et al., 2000) represents the exposure concentration at which a lifetime cancer risk equates to one excess cancer death in one million persons. This level is defined as the public health protective concentration in the Congressional House Report to the Food Quality Protection Act of 1996 in the USA. Cancer benchmark concentrations were exceeded for DDTs, heptachlor, and PCBs (See Table 16.5). The cancer hazard ratio is the ratio of the MDI for a specific contaminant relative to the cancer benchmark concentration. The cancer hazard ratio represents the extent to which average daily exposure exceeds the benchmark concentration. The cancer hazard ratio of seafood consumption... 

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