Risk factors, cancer, animal studie

There are of course many mathematically complex ways to perform a risk assessment, but first key questions about the biological data must be resolved. The most sensitive endpoint must be defined along with relevant toxicity and dose-response data. A standard risk assessment approach that is often used is the so-called divide by 10 rule . Dividing the dose by 10 applies a safety factor to ensure that even the most sensitive individuals are protected. Animal studies are typically used to establish a dose-response curve and the most sensitive endpoint. From the dose-response curve a NOAEL dose or no observed adverse effect level is derived. This is the dose at which there appears to be no adverse effects in the animal studies at a particular endpoint, which could be cancer, liver damage, or a neuro-behavioral effect. This dose is then divided by 10 if the animal data are in any way thought to be inadequate. For example, there may be a great deal of variability, or there were adverse effects at the lowest dose, or there were only tests of short-term exposure to the chemical. An additional factor of 10 is used when extrapolating from animals to humans. Last, a factor of 10 is used to account for variability in the human population or to account for sensitive individuals such as children or the elderly. The final number is the reference dose (RfD) or acceptable daily intake (ADI). This process is summarized below. 

Health Study (Gann et al., 1994) and the Health Professionals Follow-up Study (Giovannacci et al., 1993) eating red meat also emerged as a risk factor for prostate cancer. Leitzmann et al. (2004) reported that the ALA from both plant and animal sources was suggestively associated with an increased risk of advanced prostate cancer. However, total prostate cancer risk or early stage prostate cancer was not associated with ALA intake. 

Figure 26.3 illustrates a hypothetical example of interaction between intake of well-done meats, intake of dairy products, and colon cancer risk. The best candidates for interaction with meat intake and colon cancer risk are probably genetic susceptibility factors, which are discussed in detail in Section 26.4. To our knowledge, nongenetic interactions with HCA intake and colon cancer risk have not been studied. Animal studies have shown that dairy products were protective of aberrant crypts (a preneoplastic colonic lesion) induced by 2-amino-l-methyl-6-phenylimid-azo(4,5-b)pyridine (PhIP, a specific HCA). In this hypothetical example, a modest risk is observed for HCA intake and colon cancer in the total population (OR = 1.47). However, when the population is stratified according to dairy consumption, an increased risk for HCA intake is only observed in the strata of low dairy consumption (OR = 2.43), suggesting that the effect of high intake of HCAs from meat may only be relevant when intake of dairy products is low. Source Tavan et al. (2002). 

PhIP formation starts accelerating at temperatures >200°C. Recent studies have not found any correlation between color developments and HAs content in chicken (237). In pan-fried meat patties, HAs have been shown to induce bacterial mutagenicity and animal carcinogenicity and may be a risk factor for human cancer... 

Both chronic human studies and animal studies proved the causal relationship between cumulative UVR exposure and skin cancer (277), particularly non-melanoma skin cancer (NMSC). The link between the two is also evident from the fact that NMSC is most common on the head, neck, arms, and hands (278, 279). In particular, the correlation between UVR exposure and SCC seems to be very strong. Cutaneous SCC of the head and neck occurs almost exclusively on areas receiving maximal exposure (269,280). The link between BCC and cumulative exposure to UVR is not as evident (270, 281). Although BCC occurs on the face, head, and neck, unlike SCC, its distribution does not correspond well with the areas that receive maximum sun exposure (269). Case-control studies indicated that cumulative sun exposure is the most important risk factor for SCC, whereas inability to tan was the most important risk factor for BCC (270,282,283).Subsequently, it has been suggested that, for BSC, intermittent sun exposure, particularly in the childhood, may be more important than cumulative exposure (282). 

The Royal Commission on Environmental Pollution reported in 1996 that it was not aware of any study that provided firm evidence of adverse effects of contaminated land on health.10 However, the potential for health effects is real. Exposure to chemicals is a risk factor for several diseases and the International Agency for Research on Cancer has classified over 70 chemicals as human carcinogens, 60 as probable and more than 200 as possible carcinogens.11 There is evidence of an environmental influence in human diseases such as cancer,12 including geographic variation in cancer incidence in migrant populations, occupational studies and animal experiments. A number of studies also appear to suggest an association between other health effects and exposure to environmental chemicals. There are thousands of sites contaminated with hazardous chemicals with the potential to expose human populations. In the USA, the ATSDR has estimated that 46 % of the assessed National Priority List sites represent an actual hazard to health.13... 

The recommended daily intake values as estimated by the United States Environmental Protection Agency (EPA) (4) and the Centers for Disease Control (CDC) (5,6) have been used for the present calculations. For the EPA the "Acceptable Daily Intake" (ADI) for 2,3,7,8-TCDD is 1 x 10" g/kg/day. This value is based on the lowest-observed-adverse-effect-level (LOAEL) of 1 X 10 g/kg/day for a reproductive effect in rats (7,8), a 10-fold uncertainty factor because a LOAEL is used as the basis of the calculation rather than a no-observed adverse effect level (NOAEL), and an additional uncertainty factor of 100 based on the existence of lifetime animal studies and lack of knowledge of the effects in man. (4). For a 10" (1/1,000,000) cancer risk, the EPA has estimated a 95% lower-limit criteria for a lifetime intake of... 

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