Human epidemiological studies

The number of clear human epidemiologic studies is small. A total of approximately 50 compounds (c.g., benzene, vinyl chloride) and complex e.xposures (e.g., aluminum production, tobacco smoke) have sufficient data available to permit their classification as human carcinogens. The most potent human carcinogens known, the aflatoxins. are of natural origin. Their presence in food products through infestation by toxin-producing fungi constitute a serious problem in several tropical and subtropical countries. 

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. 

Aluminum does not appear to be a potential carcinogen. It has not been shown to be carcinogenic in human epidemiological studies or in animal studies after oral or inhalation exposure. 

According to the lARC, sufficient evidence of carcinogenicity for alcoholic beverages has been established in humans." Epidemiological studies clearly indicate that consumption of alcoholic beverages is causally related to cancers of the oral cavity, pharynx, larynx, esophagus, and liver. Since the lARC evaluation, evidence has accumulated for an asso-... 

Human epidemiological studies to observe carcinogenic effects are inconclusive because of small cohort size, incomplete exposure data, and insufficient latencies. ... 

Using knowledge gained from animal studies or observations from human populations, a more formal human epidemiology study may be performed. Human studies have the obvious advantage of being done on the subject of most interest, but they are time consuming and expensive, and often have many variables that are difficult to control. 

When information is derived from human epidemiological studies, it will normally be incidence of a particular disease or morbidity such as cancer or maybe the appearance of a novel disease, that is, all-or-none responses. 

Despite the widespread use, there are many health, safety, and environmental concerns associated with the use of perc. Perchloroethylene has been described as a probable human carcinogen based on both laboratory animal studies and human epidemiological studies (IARC, 1995). According to the USEPA (1998), there is a reasonable basis to conclude that there can be a health risk for cancer and some non-cancer effects to workers from the relatively high PCE exposures observed on the average in the dry cleaning industry. Risks also exist for apartment residents colocated with a perc dry cleaning facility. 

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. 

Since responses at the low dose levels of concern in routine exposures of the public cannot be measured directly in animal or human epidemiologic studies, a number of approaches have been developed to extrapolate from high to low doses. Different extrapolation approaches may fit the observed data reasonably well but lead to large differences in the projected responses at low doses (see Section 3.2.1.5.2). 

Anderson LM, Diwan BA, Fear NT, Roman E (2000) Critical windows of exposure for children s health Cancer in human epidemiological studies and neoplasms in experimental animals. Environ Health Perspect, 108(Suppl 3) 573-594. 

In the early 1960s the National Cancer Institute (NCI) developed procedures to formalize the process for the evaluation of the human risk of cancer from chemical exposures [8], This approach was based on decades of research that demonstrated that chemicals that were known to cause cancer in humans could also induce cancer in laboratory animals. The bioassay was originally envisioned as a cancer screen useful for identifying agents that would be examined in human epidemiology studies, assuming that relatively few compounds would induce tumors in animals. Despite the fact that the approach... 

Several extensive human epidemiologic studies have also been published. For example, two U.S. studies, one involving 87,245 female nurses (S23) and the other 38,910 male physicians (R5), both concluded that vitamin E supplementation was directly associated with reduced risk for ischemic heart disease. In addition, Gey and associates (G6) reported on a large cross-cultural European population which differed sixfold in age-specific mortality from CAD. The data supported their conclusions that this highly significant difference in CAD was primarily due to increased plasma vitamin E levels in those with a relatively low incidence of... 

EPA (IRIS 1996) has reviewed the human and animal carcinogenicity data on benzene. A summary of the EPA calculations of unit risk values for leukemia based on human epidemiological studies is given below. It should be noted that these values are estimates of human risk since the true human risk at low doses cannot be accurately identified. The unit risk should not be used if the air concentration exceeds 100 pg/m3 (0.031 ppm) since above this concentration the unit risk may not be appropriate. One ppm of benzene (3,190 pg/m3) exceeds the upper limit of 100 pg/m3. 

A major study (Cronkite 1986 Cronkite et al. 1984, 1985) provides a basis for a reproducible animal model. In this study, mice were exposed to 300 ppm benzene by inhalation 6 hours per day, 5 days per week for 16 weeks. This exposure regimen was selected because the authors thought it most closely paralleled likely human exposure. Human epidemiological studies in the literature reported that workers were exposed for about 15% of their life span 16 weeks represent 15% of the life span of mice. 

EPA has used cancer risk data from human epidemiological studies to derive risk factors associated with oral exposure to benzene. Oral dose levels associated with specific carcinogenic risks have been extrapolated the risk value of 2.7x 10"2 for lifetime inhalation exposure to 1 ppm was converted to a slope factor of 2.9/10"2 for oral exposure of 1 mg/kg/day, assuming identical levels of absorption of benzene following both routes of exposure. Using the method described by EPA (IRIS 1996), the drinking water levels associated with individual upper-bound estimates of 10"4, 10"5, 10"6, and 10"7 have been calculated to be lxlO 1, lxlO"2, lxlO"3, and lxlO"4 mg/L, respectively, which are equivalent to dose levels of 3x 10"3,... 

In summary, both structural and numerical chromosome aberrations have been found consistently in bone marrow cells of persons occupationally exposed to benzene. The conclusion, based on human epidemiological studies, that benzene is a human clastogen is well supported by in vivo animal studies and in vitro cell cultures and subcellular studies. Virtually all studies that looked for effects at the chromosomal level were positive when the ability to metabolize benzene was present. These experimental results are consistent with the chromosomal damage seen in exposed humans (see Sections 2.2.1.7,... 

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