Carcinogenicity known carcinogens

Klibenzanthracene, C22H 4. Crystallizes in silvery leaflets, m.p. 262 C. A polycyclic aromatic carcinogen obtained from coal tar. The 7,8 derivative, m.p. 196, is also known. 

Outside of carbon monoxide for which the toxicity is already well-known, five types of organic chemical compounds capable of being emitted by vehicles will be the focus of our particular attention these are benzene, 1-3 butadiene, formaldehyde, acetaldehyde and polynuclear aromatic hydrocarbons, PNA, taken as a whole. Among the latter, two, like benzo [a] pyrene, are viewed as carcinogens. Benzene is considered here not as a motor fuel component emitted by evaporation, but because of its presence in exhaust gas (see Figure 5.25). 

A large number of polycyclic aromatic hydrocarbons are known Many have been synthesized m the laboratory and several of the others are products of com bustion Benzo[a]pyrene for example is present m tobacco smoke contaminates food cooked on barbecue grills and collects m the soot of chimneys Benzo[a]pyrene is a carcinogen (a cancer causing substance) It is converted m the liver to an epoxy diol that can induce mutations leading to the uncontrolled growth of certain cells... 

N Nitroso amines are more often called nitrosamines and because many of them are potent carcinogens they have been the object of much investigation We encounter nitrosamines m the environment on a daily basis A few of these all of which are known carcinogens are... 

Since 1979 the use of 24 5 T has been regu lated in the United States It is likely that the United States Environmental Protection Agency will classify some dioxins as known and others as probable human carcinogens and recommend further controls be placed on processes that produce them It appears from decreasing dioxin levels in some soils that exist mg regulations are having some effect ... 

Aldehydes are important because they are temporary reservoirs of free radicals (see eqs. 11 and 12). HCHO is a known carcinogen. Nitric acid is formed by OH attack on NO2 and by a dark-phase series of reactions initiated by O3 + NO2. Nitric acid is important because it is the second most abundant acid in precipitation. In addition, in southern California it is the major cause of acid fog. 

P-Hydroxy acids lose water, especially in the presence of an acid catalyst, to give a,P-unsaturated acids, and frequendy P,y-unsaturated acids. P-Hydroxy acids do not form lactones readily because of the difficulty of four-membered ring formation. The simplest P-lactone, P-propiolactone, can be made from ketene and formaldehyde in the presence of methyl borate but not from P-hydroxypropionic acid. P-Propiolactone [57-57-8] is a usehil intermediate for organic synthesis but caution should be exercised when handling this lactone because it is a known carcinogen. 

The fused 3+ ring aromatics in petroleum include both cata- and peri-condensed stmctures (see Table 4, Fig. 8). The cata-condensed species are those stmctures where only one face is shared between rings, the peri-condensed molecules are those that share more than one face. The fused ring aromatics form the class of compounds known as polynuclear aromatic hydrocarbons (PAH) which includes a number of recognized carcinogens in the 4+ ring family (33). Because of the potential health and environmental impact of PAH, these compounds have been studied extensively in petroleum. 

The toxicity of both feeds and products must be carefully considered during the preliminary design stages (53,54) especially if the feeds or products contain known or suspected carcinogens. Special testing may even be requked prior to operation to determine the toxicity of unknown materials. 

Abbott Laboratories, which has conducted additional toxicity and carcinogenicity studies with cyclamate, a 10 1 mixture of cyclamate—saccharin, and cyclohexylamine, claimed to be unable to confirm the 1969 findings. Abbott then filed a food additive petition for cyclamate in 1973, which was denied by the FDA in 1980. In 1982, the Calorie Control Council and Abbott Laboratories filed a second food additive petition containing the results of additional safety studies (73). That petition was stiU pending as of 1996. Cyclamate is, however, allowed for use in any or all three categories, ie, food, beverage, and tabletop, in about 50 countries. Sweet n Low, known in the United States as a saccharin-based table-top sweetener, contains exclusively cyclamate in Canada. 

The word asphalt has been carelessly used in that it is not adequately differentiated from thermally degraded materials, especially coal tar and derivatives. It is essential to differentiate asphalt from these materials which contain known carcinogens and health ha2ards. For this reason, the use of cracked asphalts must be treated with caution. 

Neither the mechanism by which benzene damages bone marrow nor its role in the leukemia process are well understood. It is generally beheved that the toxic factor(s) is a metaboHte of benzene (107). Benzene is oxidized in the fiver to phenol [108-95-2] as the primary metabolite with hydroquinone [123-31-9] catechol [120-80-9] muconic acid [505-70-4] and 1,2,4-trihydroxybenzene [533-73-3] as significant secondary metabolites (108). Although the identity of the actual toxic metabolite or combination of metabolites responsible for the hematological abnormalities is not known, evidence suggests that benzene oxide, hydroquinone, benzoquinone, or muconic acid derivatives are possibly the ultimate carcinogenic species (96,103,107—112). 

BTX processing has come under steadily increasing pressure to reduce emissions and workplace exposures (see Industrial hygiene). Reductions in the permissible levels of both benzene and total aromatics (BTX) in gasoline have been legislated. Whereas all BTX components ate to be controUed, the main focus is on benzene because it is considerably mote toxic than the others and is classified as a known carcinogen (42). 

Animal and Human Toxicity. The acute toxicity of lindane depends on the age, sex, and animal species, and on the route of adrninistration. The oral LD q in mice, rats, and guinea pigs is 86, 125—230, and 100—127 mg/kg, respectively. In contrast, most of the other isomers were considerably more toxic (94,95). Some of the other toxic responses caused by lindane in laboratory animals include hepato- and nephotoxicity, reproductive and embryotoxicity, mutagenicity in some short-term in vitro bioassays, and carcinogenicity (80). The mechanism of the lindane-induced response is not known. Only minimal data are available on the mammalian toxicides of hexachlorocyclopentadiene. 

Cobalt compounds can be classified as relatively nontoxic (33). There have been few health problems associated with workplace exposure to cobalt. The primary workplace problems from cobalt exposure are fibrosis, also known as hard metal disease (34,35), asthma, and dermatitis (36). Finely powdered cobalt can cause siUcosis. There is Htfle evidence to suggest that cobalt is a carcinogen in animals and no epidemiological evidence of carcinogenesis in humans. The LD q (rat) for cobalt powder is 1500 mg/kg. The oral LD q (rat) for cobalt(II) acetate, chloride, nitrate, oxide, and sulfate are 194, 133, 198, 1700, 5000, and 279 mg/kg, respectively the intraperitoneal LD q (rat) for cobalt(III) oxide is 5000 mg/kg (37). 

The past experience of the dyestuff industry in its use of dye intermediates such as ( -naphthyl amine and benzidine (4), known human bladder carcinogens (334—343), have led to studies as to whether or not handlers of dyes are exposed to medical ha2ards such as cancer, dermatitis, and other disorders (344-360). 

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