Epidemiology, human data

According to EPA (IRIS 1999), the available human epidemiological studies lack quantitative exposure data for lead and for possible confounding exposures (e.g., arsenic, smoking). Cancer excesses in the lung and stomach of lead-exposed workers that are reported are relatively small, dose-response relationships are not demonstrated neither is there consistency in the site of cancers reported. EPA (IRIS 1999) concluded that the human data are inadequate to refute or demonstrate the potential carcinogenicity of lead exposure. 

In conclusion, phytic acid forms soluble complexes with Ca2+ at intestinal pH under a variety of conditions and fails to inhibit Ca2 bioavailability to mice in our experimental system. Despite the hazard in direct extrapolation of results obtained with animals kept on a well-defined dietary regimen to humans consuming a complex diet, many elements of which affect Ca2+ bioavailability, our data demonstrate the need for a reevaluation of the putative antinutritional properties of dietary phytate. Our further contention that adequate levels of dietary phytate may actually be beneficial due to its food preserving properties and its protection against colonic cancer will warrant a prospective epidemiological human study designed to assess the longterm effects of dietary phytate on mineral bioavailability and inflammatory bowel diseases. 

Human data include information from case reports (e.g., poisonings), clinical examinations, experimental studies in volunteers, experiences from the working environment, epidemiological studies, and meta-analyses. 

When human data of sufficient quality are available, they are preferable to animal data as no interspecies extrapolation is necessary and exposure scenarios are likely to be more realistic. However, the relatively low sensitivity of epidemiological smdies implies that it is very difficult to demonstrate the noncarcinogenicity of a substance, unless exposure conditions are exceptional and well documented. Negative human data cannot be used to override positive findings in animals, unless it has been demonstrated that the mode of action of a certain toxic response observed in animals is not relevant for humans, see Section 4.9.6. In such a case, a full justification is required. 

Valid epidemiological studies are preferable for the quantitative risk assessment of genotoxic carcinogens for the purpose of deriving a tolerable intake. If such data are available, for example in the working environment, they can be used quantitatively to convert work exposure to lifetime exposure, i.e., to convert intermittent exposure to continuous exposure (see Section 5.1 for adjustment of concentrations). However, as addressed in Chapter 3, valid human data are seldom available. 

The accumulation of human data on a wider scale, and in quantitative form, has enabled radiation epidemiology to advance from an essentially descriptive stage to an analytic one in which numerical, dose-spedfic, risk estimates have begun to be treated statistically in order to identify determinants of risk. As presently conceived, these determinants include characteristics of the radiation exposure, underlying dose-response relationships, host factors, other environmental factors, differential tissue sensitivity, time after exposure, and natural levels of incidence. 

Well documented observational, clinical and epidemiological studies in humans provide more direct information on human health effects than do studies in animal systems. However, the number of such human data is limited, and in many cases animal data are the only information available on potential adverse reproductive effects. 

In principle, well documented observational and epidemiological studies provide the most relevant information on human health effects, since they avoid extrapolation from animals to humans. However, for new chemicals, human data will not be available, mid the potential toxicity of the chemical is estimated using experimental studies. Also, human populations are heterogeneous and may be differentially... 

Although human data from epidemiological studies are useful, the majority of data on the toxicity of chemicals are gained from experimental studies in animals. Some of these studies will be carried out to understand the mechanism behind the toxicity of a particular chemical,... 

Group B2 Inadequate epidemiological evidence or no human data on the carcinogenicity of the agent and sufficient evidence in animal studies that the agent is carcinogenic... 

For any hazardous substance, estimates of the relationship of dose to response in humans are based on either animal or human data. For example, only about 20 of the approximately 300 chemical carcinogens regulated by EPA have dose-response relationships based on human data from epidemiologic studies the remainder are based on animal bioassays. In contrast, the dose-response relationships for radiation are based primarily on the results of human epidemiologic studies. 

The subcommittee evaluated human data from experimental, occupational, and epidemiologic studies data from accident reports and experimental-animal data (single and repeated exposures). The evaluations focused primarily on high-concentration inhalation exposure studies. The subcommittee s recommended SEALs are based solely on scientific data relevant to health effects. 

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