Human epidemiology

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. 

At present, human epidemiological smdies are not able to provide adequate information in this area, given the variations in resistant bacterial flora due to human drug therapy. Nevertheless, published data have suggested that experimentation in human volunteers may be an appropriate methodology. 

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. 

Therefore in practice, normally, animal toxicity data is required (see above). Of course, the differences between humans and other species must always be recognized and taken into account (see below). It may be possible to use in vitro data both from human cells and tissues as well as those from other animals to supplement the epidemiological and animal in vivo toxicity data. However, at present such data cannot replace experimental animal or human epidemiological data. The predictive use of structure-activity relationships is also possible, and it is an approach, which is becoming increasingly important. 

The fat-soluble vitamins comprise vitamins A, D, E, and K, whose biological activities are attributed to a number of structurally related compounds known as vitamers. Also included are those carotenoids that are precursors of vitamin A. Recommended dietary allowances (RDAs) based on human epidemiological and experimental animal studies have been published in the United States for vitamins A, D, E, and K (1). Other countries and international bodies have compiled similar recommendations. In the United States and Canada, fluid milk is supplemented by law with vitamin D to a level of 400 international units per quart (10 /zg/0.95 L) to meet the RDA of 10 p%. Other commodities, such as margarine, milk products, ready-to-eat breakfast cereals, and dietetic foods, are commonly supplemented with vitamins A, D, and E. Except for infant formulas, vitamin K is not added to foods. The addition of vitamins to a particular processed food is intended to provide a specific proportion of the RDA. 

Saccharin is noncaloric and noncariogenic (2,3). The safety of saccharin for public health has been the center of several controversies. In 1970, saccharin at high dietary levels was observed to increase the incidence of urinary bladder cancer in experimental rats (1,59). However, extensive human epidemiological investigations showed that use of saccharin does not significantly increase the risk of bladder cancer (5,7,11,59). Saccharin is approved for use in several countries. Its use is not permitted in Canada, and a health warning on the label of saccharin-containing foods is required in the United States (7,8,10). 

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. 

---