Carcinogen known human

Two of the earliest observations that exposure of humans to certain chemicals or substances is related to an increased incidence of cancer were made independently by two English physicians, John Hill in 1771 and Sir Percival Pott in 1776. Hill observed an increased incidence of nasal cancer among snuff users, while Pott observed that chimney sweeps had an increased incidence of scrotal cancer. Pott attributed this to topical exposure to soot and coal tar. It was not until nearly a century and a half later in 1915 when two Japanese scientists, K. Yamagiwa and K. J. Itchikawa, substantiated Pott s observation by demonstrating that multiple topical applications of coal tar to rabbit skin produced skin carcinomas. This experiment is important for two major 

Major Factors Best Estimate (%) Range of Acceptable Estimates (%) 

Source Adapted from R. Doll and R. Peto, The Causes of Cancer, Oxford Medical Publications, 1981. 

4- Butanediol dimediylsulfonate (busulfan) Cadmium and cadmium compounds Chlorambucil 

Coke oven emissions Cyclophosphamide Cyclosporin A (ciclosporin) Diethylstilbestrol (DBS) 

Dyes metabolized to benzidine Environmental tobacco smoke Erionite 

Estrogens, steroidal Ethylene oxide Hepatitis B virus Hepatitis C virus 

Human papilloma viruses some genital-mucosal types 

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Arsenic is a known human carcinogen, found in drinking water in many parts of the world. The World Health Organization (WHO) has set the upper limit for arsenic in drinking water at ten parts per billion (10 ppb). The legal limit in the United States, set by the Environmental Protection Agency (EPA) is 50 ppb. 

It is important to realize that this test is flexible and is still undergoing modification and development. Almost all the known human carcinogens have been tested and shown... 

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). 

The EPA classifies all radionuclides, including americium, as Group A (known human) carcinogens (EPA 1997b). Lifetime excess total cancer risk per unit intake or exposure for ingestion, inhalation, and external exposure to 241 Am and 243Am are included in Table 8-1. The EPA has not derived reference concentrations (RfCs) or reference doses (RfDs) for americium (IRIS 2001). 

In the USA, the National Toxicology Program has declared dioxin a known human carcinogen - but injection moulder Brevet Inc. (who manufactures medical devices from PVC) plans to challenge the action in court. Brief details are given here. 

All known human carcinogens - the substances ranked by lARC as having been causally linked to human cancers - have been shown to be capable of inducing cancers in some (but not all) species of experimental animals, with the possible exception of arsenic. Arsenic is a human carcinogen, however it has not been adequately tested in animals - so it is perhaps not a real exception to the rule. A few examples of carcinogens that are known to be active in both humans and animals are presented in Table 6.4. 

In its ninth report on known human carcinogens and reasonably anticipated human carcinogens, published in 2000, the NTP removed mention of saccharin (which had been listed in the first report, issued in 1980). The experts advising NTP reviewed a massive amount of mechanistic and epidemiological research and concluded that... 

The biochemical mechanism of ozone toxicity appears to have many similarities with those of other agents, particularly ionizing radiation, that ate known human carcinogens. 

Exposure limits Known human carcinogen. Given that no standards have been established, NIOSH (1997) recommends the most reliable and protective respirators be used, i.e., a self-contained breathing apparatus that has a full facepiece and is operated under positive-pressure or a supplied-air respirator that has a full facepiece and is operated under pressure-demand or under positive-pressure in combination with a self-contained breathing apparatus operated under pressure-demand or positive-pressure. 

Exposure limits (ppm) Known human carcinogen. NIOSH REL TWA 0.1, STEL 1, IDLH 500 OSHA PEL TWA 1, STEL 5 ACGIH TLV TWA 0.5, STEL 2.5 (adopted). 

Exposure limits Known human carcinogen. ACGIH TLV TWA 1 ppb (adopted). 

All known human carcinogens that have been smdied adequately for carcinogenicity in experimental animals have produced positive results in one or more animal species (lARC 2006). lARC (2006) also states that although this association cannot establish that aU substances that cause cancer in experimental animals also cause cancer in humans, it is biologically plausible that substances for which there is sufficient evidence of carcinogenicity in experimental animals also present a carcinogenic hazard to humans. 

Reactive chemicals are used to manufacture drugs and a proportion of these are geno-toxic. A draft guideline has been issued by the Europe and CHMP that seeks to control patient exposure to most genotoxic contaminants to below a Threshold of Toxicological concern of 1.5 xg/day. This is based on modelling data on known human carcinogens where such concentrations for specific compoimds would not be expected to increase human cancer above 1 per 10 exposed individuals. ... 

Moore RM, Jr, Wolf BS, Stein HP, et al Metabolic precursors of a known human carcinogen. Science 195 344, 1977... 

TCDD (dioxin), long considered as a very toxic chemical, was reclassified as a known human carcinogen (see also 1971). 

Gori (1991, 226) says, "to defend animal tests by saying that most of the few known human carcinogens are also carcinogens in animals is a classic non-sequitur all rats are mammals therefore all mammals are rats."... 

Chronic exposure to much lower levels has been associated with leukemia of several types as well as lymphomas, myeloma, and myelodysplastic syndrome. Recent studies have shown the occurrence of leukemia following exposures as low as 2 ppm-years. The pluripotential bone marrow stem cells appear to be a target of benzene or its metabolites and other stem cells may also be targets. Epidemiologic data confirm a causal association between benzene exposure and an increased incidence of leukemia in workers. Most organizations now classify benzene as a known human carcinogen. 

Hexavalent chromium is a known human carcinogen, however, and its commercial use is strictly regulated and highly discouraged by environmental authorities. An alternative metal to chromium in premetallized azo dyes would have to have the same color and fastness properties as chromium but without the toxicity. It has been found that iron, which is essentially nontoxic, often imparts the same desirable qualities as chromium when used in azo dyes [82,83]. This is exemplified in comparing azo dyes 44 and 45. Dyestuff 45 has the same color and fastness as 44, but does not contain chromium. Other examples of dyestuffs that use iron rather than chromium are available [82, 83]. 

Based on the evidence reviewed above, EPA has concluded that BCME is a known human carcinogen (EPA Group A). Employing the data of Kuschner et al. (1975), EPA (1988) has calculated an upper bound cancer potency factor (q ) of 220 (mg/kg/day)1. Assuming that a 70-kg adult inhales 20 m3/day, the concentrations of BCME associated with upper bound human risk levels of 10 4, 10 5, 10 6 and 10"7 are 3.4 x 10"7, 3.4 x 10"8, 3.4 x 10 9 and 3.4 x 10 10 ppm, respectively. These values, and doses which have been observed to cause cancer, are plotted in Figure 2-1. 

Carcinogenicity. A number of metals have been shown to be carcinogenic in humans or animals. Arsenic, certain chromium compounds, and nickel are known human carcinogens beryllium, cadmium, and cisplatin are probable human carcinogens. The carcinogenic action, in some cases, is thought to result from the interaction of the metallic ions with DNA (see Chapter 11 for a detailed discussion of carcinogenesis). 

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