PAH

Polycyclic aromatic hydrocarbons ,PAHs, are chemical compounds that consist of fused aromatic ring and do not contain heteroatoms or carry substituents. PAHs occur in oil, coal, and tar deposits, and are produced as byproducts of fuel burning. As a pollutant, they are of concern because some compounds have been identified as carcinogenic, mutagenic, and teratogenic. PAHs are also found in foods. Studies have shown that most food intake of PAHs comes from cereals, oils and fats. Smaller intakes come from vegetables and cooked meats.

PAH’s enter the environment mostly as releases to air from volcanoes, forest fires, residential wood burning, and exhaust from automobiles and trucks. They can also enter surface water through discharges from industrial plants and waste water treatment plants, and they can be released to soils at hazardous waste sites if they escape from storage containers. The movement of PAH’s in the environment depends on properties such as how easily they dissolve in water, and how easily they evaporate into the air. PAH’s in general do not easily dissolve in water. They are present in air as vapors or stuck to the surfaces of small solid particles. They can travel long distances before they return to earth in rainfall or particle settling. Some PAH’s evaporate into the atmosphere from surface waters, but most stick to solid particles and settle to the bottoms of rivers or lakes. In soils, PAH’s are most likely to stick tightly to particles. Some PAH’s evaporate from surface soils to air. Certain PAH’s in soils also contaminate underground water. The PAH’s content of plants and animals living on the land or in water can be many times higher than the content of PAH’s in soil or water. PAH’s can break down to longer-lasting products by reacting with sunlight and other chemicals in the air, generally over a period of days to weeks. Breakdown in soil and water generally takes weeks to months and is caused primarily by the actions of microorganisms.

You can be exposed to a substance only when you come in contact with it. You may be exposed by breathing, eating, or drinking substances containing the substance or by skin contact with it.

If you are exposed to substances such as PAH’s, many factors will determine whether harmful health effects will occur and what the type and severity of those health effects will be. These factors include the dose (how much), the duration (how long), the route or pathway by which you are exposed (breathing, eating, drinking, or skin contact), the other chemicals to which you are exposed, and your individual characteristics such as age, sex, nutritional status, family traits, lifestyle, and state of health.

PAH’s can be harmful to your health under some circumstances. Several of the PAH’s, have caused tumors in laboratory animals when they breathed these substances in the air, when they ate them, or when they had long periods of skin contact with them. Studies of people show that individuals exposed by breathing or skin contact for long periods to mixtures that contain PAH’s and other compounds can also develop cancer. Mice fed high levels of benzo[a]pyrene during pregnancy had difficulty reproducing and so did their offspring. The offspring of pregnant mice fed benzo[a]pyrene also showed other harmful effects, such as birth defects and decreased body weight. Similar effects could occur in people, but we have no information to show that these effects do occur. Studies in animals have also shown that PAH’s can cause harmful effects on skin, body fluids, and the body's system for fighting disease after both short- and long-term exposure. These effects have not been reported in people. The Department of Health and Human Services (DHHS) has determined that benz[a]anthracene, benzo[b]fluoranthene, benzo[j]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, dibenz[a,h]anthracene, and indeno[1,2,3-c,d]pyrene are known animal carcinogens. The International Agency for Research on Cancer (IARC) has determined the following: benz[a]anthracene and benzo[a]pyrene are probably carcinogenic to humans; benzo[b]fluoranthene, benzo[j]fluoranthene, benzo[k]fluoranthene, and indeno[1,2,3-c,d]pyrene are possibly carcinogenic to humans; and anthracene, benzo[g,h,i]perylene, benzo[e]pyrene, chrysene, fluoranthene, fluorene, phenanthrene, and pyrene are not classifiable as to their carcinogenicity to humans. EPA has determined that benz[a]anthracene, benzo[a]pyrene, benzo[b]fluoranthene, benzo[k]fluoranthene, chrysene, dibenz[a,h]anthracene, and indeno[1,2,3-c,d]pyrene are probable human carcinogens and that acenaphthylene, anthracene, benzo[g,h,i]perylene, fluoranthene, fluorene, phenanthrene, and pyrene are not classifiable as to human carcinogenicity. Acenaphthene has not been classified for carcinogenic effects by the DHHS, IARC, or Environmental Protection Agency(EPA).

In your body, PAHs are changed into chemicals that can attach to substances within the body. The presence of PAHs attached to these substances can then be measured in body tissues or blood after exposure to PAHs. PAHs or their metabolites can also be measured in urine, blood, or body tissues. Although these tests can show that you have been exposed to PAHs, these tests cannot be used to predict whether any health effects will occur or to determine the extent or source of your exposure to the PAHs. It is not known how effective or informative the tests are after exposure is discontinued. These tests to identify PAHs or their products are not routinely available at a doctor's office because special equipment is required to detect these chemicals.

The federal government has set regulations to protect people from the possible health effects of eating, drinking, or breathing PAHs. EPA has suggested that taking into your body each day the following amounts of individual PAHs is not likely to cause any harmful health effects: 0.3 milligrams (mg) of anthracene, 0.06 mg of acenaphthene, 0.04 mg of fluoranthene, 0.04 mg of fluorene, and 0.03 mg of pyrene per kilogram (kg) of your body weight (one kilogram is equal to 2.2 pounds). Actual exposure for most of the United States population occurs from active or passive inhalation of the compounds in tobacco smoke, wood smoke, and contaminated air, and from eating the compounds in foods. Skin contact with contaminated water, soot, tar, and soil may also occur. Estimates for total exposure in the United States population have been listed as 3 mg/day. [] -tiffany

=2.2. Polycyclic aromatic hydrocarbons in cancer=

2.2.1. Polycyclic aromatic hydrocarbons
Polycyclic aromatic hydrocarbons are ubiquitous environmental agents commonly believed to significantly contribute to human cancers. PAHs are formed in the process of incomplete combustion of organic material and are found widely in the environment, for example, in engine exhaust, cigarette smoke, soil, water and food (for a review, see Phillips 1999), and human exposure to PAHs is therefore unavoidable. Like many other carcinogens, polycyclic aromatic hydrocarbons are metabolized enzymatically to various metabolites, of which some are reactive. In the large group of enzymes involved in carcinogenic metabolism (reviewed by Williams & Phillips 2000), cytochrome P450 enzymes CYP1A1, 1A2, 1B1, and 3A4 are the most important enzymes in the metabolism of PAHs (Shimada //et al.// 1989, Shimada //et al.// 1996, reviewed by Pelkonen //et al.// 2003). PAHs undergo metabolic activation to diol-epoxides, which bind covalently to DNA. The DNA binding of activated PAHs is considered to be essential for the carcinogenic effect (for reviews, see Vähäkangas & Pelkonen 1989, Guengerich 2000). DNA adducts have been found in various human tissues (reviewed by Hemminki //et al.// 2000). In epidemiological studies, correlations between the level of PAH exposure and the number of PAH-DNA adducts have been found, including that between coke oven exposure and PAH-DNA adducts in blood cells (Harris //et al.// 1985, Haugen //et al.// 1986) and that between cigarette smoking and PAH-DNA adducts also in blood cells (for a review, see Poirier //et al.// 2000). A refined repair system has evolved to eliminate DNA adducts from the genome. PAH adducts are repaired by nucleotide excision repair (for a review, see Hoeijmakers 2001). If the adducts are left unrepaired, they may cause permanent mutations (for a review, see Boysen & Hecht 2003). If these mutations are situated at critical sites, including tumour suppressor genes or oncogenes, they may lead to cellular transformation and the development of tumours. In some cases, specific mutations found in the TP53 gene, the most commonly mutated gene in human cancers, are associated with exposure to certain carcinogens (Hernandez-Boussard & Hainaut 1998, reviewed by Hainaut & Pfeifer 2001, Vähäkangas 2003). For example, the PAHs in cigarette smoke bind preferentially to the sites called hotspot codons in TP53, where most smoking-associated mutations are also found (Pfeifer //et al.// 2002). Such studies give support to the link between DNA adducts and the cancer risk in humans.

2.2.2. Benzo(a)pyrene
According to the International Agency for Research on Cancer (IARC), there is sufficient evidence to show that BP is carcinogenic in laboratory animals, and BP is probably also carcinogenic in humans (group 2A, IARC 1983). The ability of BP to induce tumours upon local administration is well documented (for a review, see Hecht 1999). BP is metabolically activated, and the ultimate carcinogenic product is formed via a three-step process. The first step includes the formation of ( //7R,8S// )-epoxy-7,8-dihydrobenzo(a)pyrene (BaP-7,8-oxide) catalyzed by cytochrome P450 enzymes (Fig. 1, for a review, see Boysen & Hecht 2003). The second step, catalyzed by epoxide hydrolase (EH), is the conversion to ( //7R,8R// )-dihydroxy-7,8-dihydrobenzo(a)pyrene (BaP-7,8-diol). Finally, cytochrome P450 enzymes catalyze the reaction, producing four possible isomers of 7,8-diol-9,10-epoxide. Quantitatively the most important of them is ( //7R,8S// )-dihydroxy-( //9S,10R// )-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDE). BPDE, which is the ultimate carcinogen (Slaga //et al.// 1979, reviewed e.g. by Vähäkangas & Pelkonen 1989), binds to DNA at the guanine residues (Weinstein //et al.// 1976) and produces BPDE-DNA adducts. **Figure 1. The major metabolic pathway of benzo(a)pyrene leading to the ultimate carcinogen, benzo(a)pyrene-7,8-diol-9,10-epoxide (BPDE). CYP, cytochrome P450; EH, epoxide hydrolase.**

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Polycyclic aromatic hydrocarbons (PAHs) are a group of over 100 different chemicals that are formed during the incomplete burning of coal, oil and gas, garbage, or other organic substances like tobacco or charbroiled meat. PAHs are usually found as a mixture containing two or more of these compounds, such as soot.Some PAHs are manufactured. These pure PAHs usually exist as colorless, white, or pale yellow-green solids. PAHs are found in coal tar, crude oil, creosote, and roofing tar, but a few are used in medicines or to make dyes, plastics, and pesticides. **http://www.atsdr.cdc.gov/tfacts69.html** -adam