Cancer, human incidence

SHANK, R.C., BHAMARAPRAVATI, N., GORDON, J.E., WOGAN, G.N., Dietary aflatoxins and human liver cancer. IV. Incidence of primary liver cancer in two municipal populations in Thailand, Food Cosmet. Toxicol., 1972,10, 171-179. 

In some cases occupational exposures to phthalates have been associated with adverse health effects. A case-control study among a population of Danish workers employed in PVC production for 5 years or greater demonstrated a significant increase in the risk of multiple myeloma.Phthalate mixtures containing BBP have been associated with respiratory or neurological effects and cancer,increased incidence of menstrual disorders, and spontaneous abortions. " A stutfy of college students with no known exposure to phthalates found a ne tive correlation between DBP concentration and sperm density or total number of sperm. - However, this study did not consider con-founders nor did it provide ample evidence for a causal relationship of sperm characteristics to DBP levels. There were no human health data available for DEHP, DIDP, DINP, DnHP, norDnOP. 

A toxic component of braken fern, perhaps either quercetin (105) or ptaquiloside, a glucoside (106), has a mixed history of carcinogenicity. It is sometimes impHcated in an increased incidence of bladder cancer in animals and esophageal cancer in humans. Multiple other dietary components seem to either promote or interfere with its action, and the significance of braken fern in human carcinogenesis remains unproven. 

Epidemiologic studies in Japan indicate an increased risk of stomach cancer owing to consumption of broiled fish and meats (116). In the United States, stomach cancer incidence has steadily declined since the 1940s, whereas consumption of broiled food has increased (108). In addition, the average human intake of PAHs is only 0.002 of that required to produce cancer in half of animals fed. Test results are often contradictory (117) and many components of food, such as vitamin A, unsaturated fatty acids, thiols, nitrites, and even saUva itself, tend to inhibit the mutagenic activity of PAHs (118—120). Therefore, the significance of PAHs in the human diet remains unknown (121,109). 

Molybdenum, recognized as an essential trace element for plants, animals, and most bacteria, is present in a variety of metaHo enzymes (44—46). Indeed, the absence of Mo, and in particular its co-factor, in humans leads to severe debility or early death (47,48). Molybdenum in the diet has been impHcated as having a role in lowering the incidence of dental caries and in the prevention of certain cancers (49,50). To aid the growth of plants. Mo has been used as a fertilizer and as a coating for legume seeds (51,52) (see FERTILIZERS Mineral NUTRIENTS). 

The other global environmental problem, stratospheric ozone depletion, was less controversial and more imminent. The U.S. Senate Committee Report supporting the Clean Air Act Amendments of 1990 states, Destruction of the ozone layer is caused primarily by the release into the atmosphere of chlorofluorocarbons (CFCs) and similar manufactured substances—persistent chemicals that rise into the stratosphere where they catalyze the destruction of stratospheric ozone. A decrease in stratospheric ozone will allow more ultraviolet (UV) radiation to reach Earth, resulting in increased rates of disease in humans, including increased incidence of skin cancer, cataracts, and, potentially, suppression of the immune system. Increased UV radiation has also been shown to damage crops and marine resources."... 

There are many definitions of the word risk. It is a combination of uncertainty and damage a ratio of Itazards to safeguards a triplet combination of event, probability, and consequences or even a measure of economic loss or human injury in terms of both the incident likelihood and tlie magnitude of the loss or injuiy (AICliE, 1989). People face all kinds of risks eveiyday, some voluntarily and otliers involuntarily. Tlierefore, risk plays a very important role in today s world. Studies on cancer caused a turning point in tlie world of risk because it opened tlie eyes of risk scientists and healtli professionals to tlie world of risk assessments. 

Hazard identification is defined as tlie process of determining whetlier human exposure to an agent could cause an increase in the incidence of a health condition (cancer, birtli defect, etc.) or whetlier exposure to nonliumans, such as fish, birds, and otlier fonns of wildlife, could cause adverse effects. Hazard identification cliaracterizes tlie liazard in terms of tlie agent and dose of the agent. Since tliere are few hazardous chemicals or hazardous agents for wliich definitive exposure data in humans exists, tlie identification of health hazards is often characterized by the effects of health hazards on laboratory test animals or other test systems. ... 

As stated before, it is not practical to test in the range of such a low incidence. In fact, laboratories conduct animal tests at high doses to increase the likelihood of inducing cancer in a portion of a test population. Thus, to apply the results of animal tests to human exposures, the data from the high doses used in the tests must be extrapolated to the low doses of public concern. 

Kaposi sarcoma (KS) - an angiogenic-inflammatory neoplasm - is the most prevalent cancer in HIV-infected patients and its appearance is preceded by infection with human Heipesvitus-8 (HHV-8). Although chemotherapy has become the treatment of choice approved by the FDA, there are also good response rates in patients treated with IFN-a. Fortunately, today highly active antiretroviral therapy (HAART) has dramatically decreased the incidence of KS in AIDS patients. 

The initial concern for the possible hazard to humans exposed to 2,4,5-T was precipitated by teratologic studies conducted by Bionetics Research Institute under contract from The National Cancer Institute (2). In these studies, large doses of 2,4,5-T were administered to pregnant rats and mice for nine of the 21 days of pregnancy. The incidence of fetal abnormalities was slightly higher in the treated animals than in control animals. Later tests indicated that these abnormalities (cleft palate) may have been caused by 27 8 ppm of 2,3,7,8-tetrachloro-dibenzo-p-dioxin present as a contaminant in the 2,4,5-T sample used in the Bionetic study (3). After the results of the study were made known, the Panel on Herbicides of the President s Science Advisory Committee studied the total 2,4,5-T situation. The report of this committee was published in March, 1971 (4). 

The Chemical Substances Threshold Limit Values Committee classifies certain substances found in the occupational environment as either confirmed or suspected human carcinogens. The present listing of substances that have been identified as carcinogens takes two forms those for which a TLV has b n assigned and those for which environmental and exposure conditions have not been sufficiently defined to assign a TLV. Where a TLV has been assigned, it does not necessarily imply the existence of a biological threshold however, if exposures are controlled to this level, we would not expect to see a measurable increase in cancer incidence or mortality. 

Babson proposed a-naphthyl phosphate as an essentially specific substrate for the activity of prostatic acid phosphatase in serum (104). However Marshall, Price, and Amador found that this substrate is not specific for the prostatic enzyme because urine of human females contain 50 times more acid a-naphthyl phosphatase than male serum and 50% as much activity as male urine. Platelets have significant activity and the serum activity can increase to abnormal values following clotting. These workers also observed elevated activities in females with skeletal metastases of the breast. In 50 hospitalized male patients who had no evidence of prostatic cancer and 25 hospitalized female patients, the incidence of false positive results was 12%, a magnitude sufficient to preclude meaningful clinical interpretation (105). 

An update of a previous study (Axelson et al. 1978), Axelson (1986) evaluated an expanded cohort of 1,424 men (levels of trichloroethylene exposure inferred from measured urinary metabolite concentrations) and found a significant increase in incidences of bladder cancer and lymphomas, and a lower than expected incidence of total cancer mortality. A further update of this work (Axelson et al. 1994) expanded the cohort to include 249 women, tracking cancer morbidity over 30 years, and found no correlation between exposure concentration or exposure time and cancer incidence at any site. The highest standardized incidence ratio noted in this study was 1.56 (95% Cl of 0.51-3.64) for 5 cases of non-Hodgkin s lymphoma observed in men. Although four of these cases occurred in persons exposed for at least 2 years, and 3 cases had a latency of 10 years or more, urinary levels of TCA showed that 4 of the 5 cases were exposed to the lowest levels of trichloroethylene (urinary levels of TCA 0-49 mg/L). The study authors mentioned that a urinary TCA level below 50 mg/L corresponds to a trichloroethylene exposure concentration of about 20 ppm. The study authors concluded that "this study provides no evidence that trichloroethylene is a human carcinogen, i.e., when the exposure is as low as for this study population."... 

Cancer. Workers who have been exposed to trichloroethylene show no higher incidence of cancer than controls in numerous epidemiologic studies (Axelson et al. 1978 Hardell et al. 1981 Malek et al. 1979 Novotna et al. 1979 Paddle 1983 Spirtas et al. 1991 Tola et al. 1980). Studies that did show an increased incidence of specific cancers in exposed workers were complicated by exposures to other chemicals, including known human carcinogens (Antilla et al. 1995 Blair et al. 1979 Hardell et al. 1994 Henschler et al. 1995). 

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