Carcinogenic health effect models

It is presumed that the effect of carcinogenic materials is to produce critical cell damage. Thus, carcinogenic health effects models generally are dose (i.e., integrated exposure) models, not exposure models. The lack of firm statistical bases often leads to the adoption of nonthreshold, linear models, even though thresholds and nonlinear effects might be expected. 

If linear (dose) models without thresholds are to be used for carcinogen (or other) risk assessment, estimation of exposure at specified levels becomes irrelevant to risk assessment or, at least, its use is nonintuitive. For example, a carcinogen risk analysis may be based on a linear, nonthreshold health effects model. The total health risk would thus be proportional to the long-term exposure summed for all affected people for the identified period, and exposure of many people at low concentrations would be equivalent to exposure of a few to high concentrations. The atmospheric dispersion that reduces concentrations would also lead to exposure of more people therefore, increments... 

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. 

Occupational and toxicological studies have demonstrated adverse health effects from exposure to toxic contaminants. Emissions data from stationary and mobile sources are used in an atmospheric dispersion model to estimate outdoor concentrations of 148 toxic contaminants for each of the 60,803 census tracts in the contiguous United States for 1990. Approximately 10% of all census tracts had estimated concentrations of one or more carcinogenic HAPs at a greater than l-in-10,000 risk level. Twenty-two pollutants with chronic toxicity benchmark concentrations had modeled concentrations in excess of these benchmarks, and approximately 200 census tracts had a modeled concentration 100 times the benchmark for at least one of these pollutants. This comprehensive assessment of air toxics concentrations across the United States indicates hazardous air pollutants may pose a potential public health problem (Woodruff et al., 1998). 

Metal Emission Limits. Limits for metals, both carcinogenic and noncarcinogenic, are based on an adjusted stack height. Failure to meet these limits requires risk assessments using site specific factors and modeling to establish limits for each metal. The assessments are based on the probability of developing adverse health effects or cancer, based on an inhalation exposure pathway to maximum exposed individuals located near the incinerator (see Hazard ANALYSIS AND RISKASSESSL nt). 

Since the linear model consistently predicts the highest response frequency per unit dose in very low dose range, it is usually the most conservative or least likely to underestimate human health risk. It is often recommended by regulating agencies to determine the risk of known or suspected human carcinogens. For non-carcinogens, the quadratic model that predicts a threshold dose at which there is no effect is often used. 

Curcumin (diferuloyl methane) is the main pigment of turmeric. It is widely used as a colorant and preservative agent. No data regarding its daily intake in western countries are available intake may reach 80 to 200 mg in adult Indians. To date, no study has explored the effect of curcumin consumption on the incidence of diseases, but many beneficial effects on health have been reported in cell and animal models. These include anti-carcinogenic, anti-diabetic, anti-atherosclerotic, and anti-Alzheimer s disease properties. ... 

REACH aims to protect both the environment and human health from the industrial chemicals used in Europe, which refer to tens of thousands of substances. In this case, the ideal systems to be evaluated are human health and environment. However, the legislation defines a series of models, which can be used to assess the effects on these two major systems. Animal models are quite often mentioned, in case of toxicity studies and bioaccumulation. Examples of such models are models using rat and fish. Rat and mouse, typically, are used as models for human health, and fish is useful for environmental endpoints. However, it is well recognized that humans are different from rodents for a series of biochemical processes. To study carcinogenicity, for instance, a battery of tests is common, using rat and mouse, both male and female animals. Differences are often found in the different rodent experiments, and this highlights the problems in extrapolating results to humans. Still, in vivo experiments are a fundamental way to study toxicity. 

---