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POLYNUCLEAR AROMATIC HYDROCARBONS

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Some, but not all, polynuclear aromatic hydrocarbons (PAHs) or their metabolic intermediates are mutagens and/or carcinogens (Ellenhorn & Barceloux, 1988; Holbrook, 1990; Pike, 1992; ATSDR, 1993).

Specific Substances

    A) CONSTITUENTS OF THE GROUP
    1) PAH
    2) PAHs
    3) Polycyclic Aromatic Hydrocarbons
    4) Polynuclear Aromatic Hydrocarbons
    5) Polycyclic Organic Matter (POM)
    Benzo(a)anthracene
    1) CAS 56-55-3
    Benzo(a)pyrene
    1) CAS 50-32-3
    Benzo(e)pyrene
    1) CAS 192-97-2
    Benzo(k)fluoranthene
    1) CAS 207-08-9
    Benzo(g,h,i)perylene
    1) CAS 191-24-2
    Chrysene
    1) CAS 218-01-9
    Coronene
    1) CAS 191-07-1
    Dibenz(a,h)acridine
    1) CAS 226-26-8
    Dibenz(a,h)anthracene
    1) CAS 53-70-3
    7H-Dibenzo(c,g)carbazole
    1) CAS 194-59-2
    7,12-Dimethylbenz(a)anthrancene
    1) CAS 57-97-6
    2) CAS 56-56-4
    3-Methylcholanthrene
    1) CAS 56-49-5
    Pyrene
    1) CAS 129-00-0
    REFERENCES
    1) ATSDR, 1993; Ellenhorn & Barceloux, 1988; Pike, 1992

Available Forms Sources

    A) FORMS
    1) Polynuclear Aromatic Hydrocarbons (PAHs; polycyclic aromatic hydrocarbons) contain only carbon and hydrogen atoms and are made up of three or more benzene rings fused together (Ellenhorn & Barceloux, 1988; Pike, 1992; ATSDR, 1993).
    2) PAHs are low volatility solids at room temperature (ATSDR, 1993).
    3) There are hundreds of PAHs (Ellenhorn & Barceloux, 1988; ATSDR, 1993).
    B) SOURCES
    1) NATURAL SOURCES: PAHs are components of most fossil fuels and are ubiquitous in the natural environment (ATSDR, 1993; Ellenhorn & Barceloux, 1988). They are released in forest fires and volcanic eruptions, and are also naturally synthesized by such crops as lentils, rye, and wheat (Pike, 1992; ATSDR, 1993).
    2) ANTHROPOGENIC (Ellenhorn & Barceloux, 1988; Boulos & von Smolinski, 1988; ATSDR, 1993):
    a) Most environmental PAHs occur from incomplete combustion or pyrolysis of fossil fuels (Ellenhorn & Barceloux, 1988; Holbrook, 1990). Stationary fuel sources are responsible for over 97 percent of PAH emissions (Pike, 1992). Over 87 percent of total PAH emissions are due to open trash burning, coke ovens, and residential furnaces (Pike, 1992). PAHs can be found in solid wastes (Warshawsky, 1999).
    b) EMISSIONS SOURCES (Karahalil et al, 1999; Pike, 1992)
    1) Cigarette Smoke
    2) Coal Gasification Plants
    3) Coal Refuse Fires
    4) Coal Tar Pitch
    5) Coke Production
    6) Creosote
    7) Engine exhaust
    8) Engine oil, used
    9) Forest/Agricultural Refuse Burning
    10) Fuel Burning and Open Burning of Refuse
    11) Industries Using or Producing Coal, Tar, Coke, Asphalt (bitumen)
    12) Mobile Sources, Gasoline
    13) Restaurants and Smokehouses
    14) Roof Tarring
    15) Sidewalk Tarring
    16) Vehicle Disposal, Open Burning
    17) Wood-Burning Fireplaces, etc.
    c) WASTE DEPOSITS: In developed countries, waste deposits from former production of lighting and heating gas from coal or oil contain large concentrations of PAHs. Such plants were generally in operation from the 1800s through the 1950s, when they were phased out in favor of natural gas use. More than 1000 such plants were formerly active in the US, concentrated in the Eastern and Midwestern parts of the country (Pike, 1992).
    3) FOODS: charring, barbecuing, smoking of foods; foodstuffs such as coffee, roasted peanuts; refined vegetable oils, crude coconut oil, heavily smoked ham; seafood and various agricultural products (from atmospheric contamination and penetration into water systems)
    4) OTHER - smoke from cigarettes, cigars, pipes, marijuana. Approximately 150 PAHs have been isolated in tobacco and marijuana smoke (Lee et al, 1976).
    5) OTHER - soils from creosotiny plants may contain PAHs (Guerin, 1999).
    C) USES
    1) Benzo(a)pyrene (CAS 50-32-3) is generally used as a model compound for PAH exposure (Holbrook, 1990; Ellenhorn & Barceloux, 1988).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) In general, PAHs have a low order of acute toxicity in humans.
    B) PAHs and other compounds found in COAL TAR can produce a variety of non-cancer effects with chronic exposure. Chronic effects include:
    1) EYES - Photosensitivity and irritation.
    2) RESPIRATORY - Irritation with cough and bronchitis.
    3) MOUTH - Leukoplakia.
    4) DERMAL - "Coal tar warts" (precancerous lesions enhanced by UV light exposure), erythema, dermal burns, photosensitivity, acneiform lesions, irritation.
    5) HEPATIC/RENAL - Mild hepatotoxicity or mild nephrotoxicity (animals).
    6) GENITOURINARY - Hematuria.
    C) CANCER is the most significant PAH toxicity endpoint.
    1) Increased incidences of cancers of the skin, bladder, lung and gastrointestinal tract have been described in PAH-exposed workers.
    0.2.6) RESPIRATORY
    A) Irritation, chronic cough, bronchitis, and bronchogenic cancer can occur with chronic exposure.
    0.2.8) GASTROINTESTINAL
    A) Leukoplakia and cancers of the lip and oral cavity can develop with chronic exposure.
    0.2.9) HEPATIC
    A) Mild hepatotoxicity has been reported in PAH-exposed rats.
    0.2.10) GENITOURINARY
    A) Hematuria, kidney and bladder cancer are possible effects of chronic exposure. Mild nephrotoxicity has been documented in PAH-exposed rats.
    0.2.13) HEMATOLOGIC
    A) Agranulocytosis, anemia, leukopenia, and pancytopenia developed in rats chronically fed PAHs.
    0.2.14) DERMATOLOGIC
    A) PRECANCEROUS LESIONS - "Coal tar warts" (precancerous lesions enhanced by UV light exposure), erythema, dermal burns, acneiform lesions, photosensitization and cancer may develop following chronic exposure.
    0.2.19) IMMUNOLOGIC
    A) An effect of PAHs on immune function might aid in the development of neoplasms. A number of PAH compounds are immunotoxic, and some suppress selective components of the immune system.
    0.2.20) REPRODUCTIVE
    A) In experimental animal studies, PAHs and metabolites cross the placenta. Female offspring of experimental animals exposed to PAHs during pregnancy have a decrease in the number of functional oocytes, sometimes such that they are infertile.
    B) PAHs are lipophilic and are excreted in breast milk, allowing for secondary exposure of nursing infants, although the potential significance of such exposure has not been determined.
    0.2.21) CARCINOGENICITY
    A) Cancer is the most significant PAH toxicity endpoint. Some, but not all, PAHs are carcinogens. Certain PAH parent compounds are weak carcinogens, only becoming potent carcinogens after undergoing metabolism. Chronic or repeated exposure increases the likelihood of cancer initiation, as well as the potential for metabolism of a PAH procarcinogen to a carcinogen.
    B) Increased incidences of skin, bladder, lung, and possibly gastrointestinal tract cancers have been described in PAH-exposed workers, particularly associated with coal carbonization, coal gasification, and coke oven work.

Laboratory Monitoring

    A) PAHs have been determined in the blood and tissues of experimental animals. Direct biologic measurement of PAHs currently is not clinically useful or cost-effective. Indirect methods of determining exposure are available but have not yet proven clinically useful (ATSDR, 1990).
    B) Acute respiratory effects in persons at PAH-containing workplaces are typically due to other toxic agents at the worksite (ATSDR, 1990). Arterial blood gases, chest x-ray, and other monitoring may be indicated, based on the patient's presentation and the exposure characteristics.
    C) Chronic effects, particularly cancer, are more common than acute toxicity. Routine monitoring and physical assessments (e.g, complete blood count, hepatic and renal function tests, chest xray and pulmonary function tests, dermal assessments) of individuals with significant exposure is recommended, even in the absence of symptoms (ATSDR, 1990).

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Toxicity from these substances involves chronic exposure, toxicity after acute ingestions is unlikely and gastric decontamination is generally NOT indicated.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    B) Inhalational exposure to PAHs may be complicated by exposure to other substances which produce acute respiratory and systemic effects. Treat according to clinical presentation and exposure history.
    1) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents.
    2) Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    3) Monitor arterial blood gases and/or pulse oximetry, pulmonary function tests, and chest x-ray in patients with significant exposure.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    2) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.
    3) Some chemicals can produce systemic poisoning by absorption through intact skin. Carefully observe patients with dermal exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.

Range Of Toxicity

    A) The minimum lethal human dose to this agent has not been delineated.
    B) The maximum tolerated human exposure to this agent has not been delineated.

Clinical Effects

Summary Of Exposure

    A) In general, PAHs have a low order of acute toxicity in humans.
    B) PAHs and other compounds found in COAL TAR can produce a variety of non-cancer effects with chronic exposure. Chronic effects include:
    1) EYES - Photosensitivity and irritation.
    2) RESPIRATORY - Irritation with cough and bronchitis.
    3) MOUTH - Leukoplakia.
    4) DERMAL - "Coal tar warts" (precancerous lesions enhanced by UV light exposure), erythema, dermal burns, photosensitivity, acneiform lesions, irritation.
    5) HEPATIC/RENAL - Mild hepatotoxicity or mild nephrotoxicity (animals).
    6) GENITOURINARY - Hematuria.
    C) CANCER is the most significant PAH toxicity endpoint.
    1) Increased incidences of cancers of the skin, bladder, lung and gastrointestinal tract have been described in PAH-exposed workers.

Heent

    3.4.3) EYES
    A) IRRITATION - Photosensitivity and irritation may occur following chronic exposure (ATSDR, 1990; ATSDR, 1993). Exposure to creosote (contains PAHs) has produced photosensitivity and irritation (Grant, 1986).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) ISCHEMIA
    1) WITH POISONING/EXPOSURE
    a) One study examined the relation between exposure to polycyclic aromatic hydrocarbons (PAH; coal tar and benzo(a)pyrene) and mortality from ischemic heart disease (IHD; 418 cases) in a cohort of 12,367 male asphalt workers from 7 countries. The average duration of follow-up was 17 years (+/- 9 years). There was approximately 60% increase in risk of mortality from IHD between the highest and the lowest PAH-exposure groups, indicating an exposure-response relation. Risk of fatal IHD was positively associated with cumulative and average benzo(a)pyrene exposure indices. The highest relative risk for fatal IHD (1.64 [95% CI = 1.13-2.38]) was observed for average benzo(a)pyrene exposures of 273 ng/m(3) or higher. The relative risk for coal tar exposure was similar to these results. In the highest PAH-exposure group, sensitivity analysis showed that even after adjustment for possible confounding by smoking, approximately 20% to 40% excess risk in IHD would be observed (Burstyn et al, 2005). This study was not able to control for all possible sources of confounding and bias.

Respiratory

    3.6.1) SUMMARY
    A) Irritation, chronic cough, bronchitis, and bronchogenic cancer can occur with chronic exposure.
    3.6.2) CLINICAL EFFECTS
    A) IRRITATION SYMPTOM
    1) Irritation with cough and bronchitis may develop with chronic exposure (ATSDR, 1993).

Gastrointestinal

    3.8.1) SUMMARY
    A) Leukoplakia and cancers of the lip and oral cavity can develop with chronic exposure.
    3.8.2) CLINICAL EFFECTS
    A) LEUKOPLAKIA
    1) Leukoplakia can develop with chronic exposure (ATSDR, 1993).

Hepatic

    3.9.1) SUMMARY
    A) Mild hepatotoxicity has been reported in PAH-exposed rats.
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEPATIC NECROSIS
    a) Elevated liver function tests and histopathologic abnormalities have been reported in PAH-exposed rats (Yoshikawa et al, 1985) Yoshikawa et al, 1987).

Genitourinary

    3.10.1) SUMMARY
    A) Hematuria, kidney and bladder cancer are possible effects of chronic exposure. Mild nephrotoxicity has been documented in PAH-exposed rats.
    3.10.2) CLINICAL EFFECTS
    A) BLOOD IN URINE
    1) Hematuria may occur following chronic exposure (ATSDR, 1990).
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) NEPHROSIS
    a) Mild nephrotoxicity, indicated by decreased kidney size, congestion, and renal cortical hemorrhages, has occurred in PAH-exposed rats (Yoshikawa et al, 1985) Yoshikowa et al, 1987).

Hematologic

    3.13.1) SUMMARY
    A) Agranulocytosis, anemia, leukopenia, and pancytopenia developed in rats chronically fed PAHs.
    3.13.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) CHRONIC TOXICITY
    a) Agranulocytosis, anemia, leukopenia, and pancytopenia developed in rats fed PAHs in a chronic toxicity study (Pike, 1992).

Dermatologic

    3.14.1) SUMMARY
    A) PRECANCEROUS LESIONS - "Coal tar warts" (precancerous lesions enhanced by UV light exposure), erythema, dermal burns, acneiform lesions, photosensitization and cancer may develop following chronic exposure.
    3.14.2) CLINICAL EFFECTS
    A) PRECANCEROUS HYPERPLASIA
    1) "Coal tar warts" (precancerous lesions enhanced by UV light exposure) can develop following chronic exposure (ATSDR, 1993).
    B) SKIN IRRITATION
    1) Erythema and dermal burns may develop following chronic exposure (ATSDR, 1993).
    C) ACNE
    1) Pilosebaceous reactions have been reported from chronic occupational exposure to PNAs (ATSDR, 1990).
    D) PHOTOSENSITIVITY
    1) Dermal photosensitization can occur from chronic exposure (ATSDR, 1990).

Immunologic

    3.19.1) SUMMARY
    A) An effect of PAHs on immune function might aid in the development of neoplasms. A number of PAH compounds are immunotoxic, and some suppress selective components of the immune system.
    3.19.2) CLINICAL EFFECTS
    A) DISORDER OF IMMUNE FUNCTION
    1) A number of PAH compounds are immunotoxic, and some suppress selective components of the immune system (White, 1986).
    2) PAHs have been shown to cause single strand breaks in DNA of T- and B-lymphocytes and granulocytes of automobile emission inspectors and incineration workers (Oh et al, 2005).
    3) Coke oven workers exposed to a range of 0.2 to 50 mcg/m(3) benzo(a)pyrene had significantly depressed levels of IgG and IgA, compared with cold-rolling mill workers (Szczeklik et al, 1994).
    4) An effect of PAHs on immune function might aid in the development of neoplasms (Boulos & von Smolinski, 1988).

Reproductive

    3.20.1) SUMMARY
    A) In experimental animal studies, PAHs and metabolites cross the placenta. Female offspring of experimental animals exposed to PAHs during pregnancy have a decrease in the number of functional oocytes, sometimes such that they are infertile.
    B) PAHs are lipophilic and are excreted in breast milk, allowing for secondary exposure of nursing infants, although the potential significance of such exposure has not been determined.
    3.20.2) TERATOGENICITY
    A) CONGENITAL ANOMALY
    1) The female offspring of experimental animals exposed to PAHs during pregnancy have a decrease in the number of functional oocytes, sometimes such that they are infertile (ATSDR, 1990; ATSDR, 1993).
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY DISORDER
    1) Placentas of mothers who smoked had increased activities of enzymes which biotransform benzo[a]pyrene to toxic metabolites, possibly indicating that the embryo or fetus of mothers who smoke may be at increased risk of exposure to toxic products of benzo[a]pyrene biotransformation (Sanyal et al, 1993). The increase in enzyme activity was highly variable.
    B) PARENTAL PRECONCEPTIONAL EXPOSURE
    1) In a case control study, the association of parental exposure to polycyclic aromatic hydrocarbons (PAH) during the 5-year period before birth and the development of childhood brain tumors was evaluated. Paternal occupational exposure to PAH increased the risk of all childhood brain tumors (OR 1.3; 95% CI 1.1 to 1.6) and astroglial tumors (OR 1.4; 95% CI 1.1 to 1.7). Paternal smoking was also associated with an increased risk of astroglial tumors (OR 1.4). Maternal smoking or maternal occupational exposure to PAH before conception or during pregnancy was not associated with any type of childhood brain tumors (Cordier et al, 2004).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) PAHs are lipophilic and are excreted in breast milk, allowing for secondary exposure of nursing infants (ATSDR, 1993), although the potential significance of such exposure has not been defined.
    2) Tobacco smoking was found to significantly contribute to the PAH contamination of milk in a study of 32 urban and rural Italian women (Zanieri et al, 2007).
    3.20.5) FERTILITY
    A) ANIMAL STUDIES
    1) The female offspring of experimental animals exposed to PAHs during pregnancy have a decreased number of functional oocytes and may be infertile (ATSDR, 1990; ATSDR, 1993).

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) Cancer is the most significant PAH toxicity endpoint. Some, but not all, PAHs are carcinogens. Certain PAH parent compounds are weak carcinogens, only becoming potent carcinogens after undergoing metabolism. Chronic or repeated exposure increases the likelihood of cancer initiation, as well as the potential for metabolism of a PAH procarcinogen to a carcinogen.
    B) Increased incidences of skin, bladder, lung, and possibly gastrointestinal tract cancers have been described in PAH-exposed workers, particularly associated with coal carbonization, coal gasification, and coke oven work.
    3.21.3) HUMAN STUDIES
    A) SUMMARY
    1) Cancer is the most significant PAH toxicity endpoint (Ellenhorn & Barceloux, 1988; Holbrook, 1990; ATSDR, 1993). Some, but not ALL, PAHs are carcinogens (ATSDR, 1993; Holbrook, 1990; Ellenhorn & Barceloux, 1988; Pike, 1992).
    2) Certain PAH parent compounds are weak carcinogens, only becoming potent carcinogens after undergoing metabolism (Holbrook, 1990; ATSDR, 1993).
    3) Chronic or repeated exposure increases the likelihood of cancer initiation, as well as the potential for metabolism of a PAH procarcinogen to a carcinogen (Holbrook, 1990).
    4) Variables such as gender, age, and pregnancy may influence the carcinogenicity of PAHs (Boulos & von Smolinski, 1988).
    B) SPECIFIC AGENT
    1) COAL TAR AND BYPRODUCTS-ASSOCIATED CANCERS (ATSDR, 1990; ATSDR, 1993) -
    a) "Coal Tar Warts" with progression to cancer
    b) Bronchogenic cancer
    c) Buccal-pharyngeal cancer
    d) Cancer of the lip
    C) CARCINOMA
    1) Studies have noted increased lung cancer in coal carbonization, coal gasification, aluminum reduction plant, and coke oven workers exposed to PAHs (Gibbs & Horowitz, 1979; Gibbs, 1985; Ellenhorn & Barceloux, 1988; ATSDR, 1993).
    2) The risk of dying from lung cancer was related to cumulative exposure to PNA's in aluminum workers, measured as benzene-soluble coal-tar pitch volatiles, after controlling for the effects of smoking. The lifetime excess risk was 2.2% after 40 years exposure at the current Canadian standard of 0.2 mg/m(3) (Armstrong et al, 1994).
    3) CIGARETTE SMOKE - Benzo(a)pyrene constitutes approximately 1% of the carcinogenic effect of cigarette smoke condensate (Pike, 1992).
    D) BRAIN TUMORS
    1) In a case control study, the association of parental exposure to polycyclic aromatic hydrocarbons (PAH) during the 5-year period before birth and the development of childhood brain tumors was evaluated. Paternal occupational exposure to PAH increased the risk of all childhood brain tumors (OR 1.3; 95% CI 1.1 to 1.6) and astroglial tumors (OR 1.4; 95% CI 1.1 to 1.7). Paternal smoking was also associated with an increased risk of astroglial tumors (OR 1.4). Maternal smoking or maternal occupational exposure to PAH before conception or during pregnancy was not associated with any type of childhood brain tumors (Cordier et al, 2004).
    E) ROUTE OF EXPOSURE
    1) GENITOURINARY TRACT -
    a) The first occupational cancer described by Dr Percival Pott in 1775 was that of scrotal cancer in chimney sweeps exposed to PAHs in soot and ash (ATSDR, 1993; Ellenhorn & Barceloux, 1988).
    b) Increased incidences of bladder cancer or increased risk of mortality due to kidney cancer have been reported in other PAH-exposed workers, particularly in association with coal tar exposure, coke oven emissions, and in aluminum reduction plants (Redmond et al, 1972; Rockette & Arena, 1983; Gibbs, 1985; IARC, 1987; Proctor et al, 1989; ATSDR, 1990; ATSDR, 1993; US DHHS, 1994).
    2) GASTROINTESTINAL TRACT -
    a) An increased risk of death (not statistically significant) due to stomach cancer, colon cancer, and an excess of pancreatic cancer were reported in individuals who worked in some aluminum reduction plant operations (Rockette & Arena, 1983).
    3) HEMATOPOIETIC SYSTEM -
    a) Leukemia (inconclusive) and lymphoma are possible effects of chronic exposure (Rockette & Arena, 1983; ATSDR, 1990).
    4) SKIN CANCER -
    a) Skin cancer has been associated with chronic exposure to coal tar or coal tar pitches (IARC, 1987).
    5) SEWAGE SLUDGE -
    a) Benzo(a)pyrene constitutes approximately 23% of the carcinogenic effect of sewage sludge extracts (Pike, 1992).
    3.21.4) ANIMAL STUDIES
    A) SYSTEMIC EFFECTS
    1) Benzo(a)pyrene, first isolated from coal tar in the 1930's, is carcinogenic when applied to the skin of experimental animals (ATSDR, 1993; Ellenhorn & Barceloux, 1988).
    2) Skin, lung, liver, and gastric cancer have been produced in laboratory animals by administration of PAHs (Ellenhorn & Barceloux, 1988; ATSDR, 1993; US DHHS, 1994).
    3) Flue gas condensate from residential coal-fired furnaces caused lung carcinomas and sarcomas in chronically exposed rats (Grimmer et al, 1987).
    4) Dose-dependent increases in bronchiole-alveolar adenomas were produced in female mice by inhalation of exhausts rich in polynuclear aromatic hydrocarbons, in a 10-month exposure to equivalents of 50 and 90 mcg/m(3) PAHs. Squamous-cell carcinomas were also seen in the high-dose group (Schulte et al, 1994).
    5) Tumors produced by PAHs are predominantly caused by benzo(a)pyrene, alone, or in combination with dibenz(a,h)anthracene (Pfeiffer, 1977).
    6) Polycyclic aromatic hydrocarbon compounds with more than 3 benzene rings derived from PAHs may be the most potent carcinogens in condensates from gasoline engine exhaust (Grimmer et al, 1984).
    7) In used engine oil, PAHs with four or more benzene rings make up only about 1.14% of the oil, but account for about 70% of the carcinogenic effects in experimental animals (Grimmer et al, 1982).
    8) SYNERGY - Cancer induction between PAHs and other chemicals may have a synergistic relationship (Boulos & von Smolinski, 1988).
    9) Dose-dependent increases in bronchiole-alveolar adenomas were produced in female mice by inhalation of exhausts rich in polynuclear aromatic hydrocarbons, in a 10-month exposure to equivalents of 50 and 90 mcg/m(3) PAHs. Squamous-cell carcinomas were also seen in the high-dose group (Schulte et al, 1994).

Genotoxicity

    A) CYTOGENETIC MARKERS OF HUMAN PAH EXPOSURE - Cells containing high frequencies of chromosomal aberrations were a sensitive marker for exposure to PAHs in coke oven and graphic electrode plant workers, compared with unexposed controls. There was no relation between cytogenetic findings and levels of benzo(a)pyrene-hemoglobin adducts (Buchet et al, 1995).
    1) Arylamines derived from carcinogenic PAHs are mutagenically activated through S9-mediated metabolism of the related amine (Fu et al, 1982).
    2) Nitro-PAH derivatives are potent bacterial mutagens. The mutagenic activity is dependent on enzymatic reduction of the nitro group and may require oxidative metabolism (Grosovsky et al, 1999; Rosenkranz & Mermelstein, 1985).
    3) In cultured human cells, benzo(a)pyrene and 7,12-demethylbenz(a)anthracene only caused a significant increase in T6 guanine-resistant mutations in the presence of cultured rat hepatocytes (Tong et al, 1981).
    4) Nitrated PAHs have caused dose-dependent cell transformations in Syrian hamster embryo cells (DiPaolo et al, 1983). Metabolic reduction of the nitro- group on PAHs may be involved in their mutagenic effects.
    5) Persons with a high degree of inducibility of the enzyme, aryl hydrocarbon hydroxylase, may be a high-risk population (ATSDR, 1993).
    B) A cross-sectional study evaluated the potential for exposure to PAHs to induce oxidative DNA damage in coke-oven workers (n=119), employed at an iron-steel factory. This study could not find clear evidence that PAH exposure induces oxidative DNA damage (Zhang et al, 2003).
    C) MUTAGENIC INTERMEDIATES -
    1) The PAH metabolic intermediates, diol-epoxides, are presumably mutagenic and can react to form DNA adducts, which may affect normal cellular replication (ATSDR, 1993; Ellenhorn & Barceloux, 1988; Pike, 1992; Amin et al, 1993; Ronai et al, 1994).
    D) LACK OF EFFECT
    1) Amongst a small group of Swedish road pavers exposed to asphalt fumes, there were no significant increases in sister chromatic exchanges or micronuclei in peripheral blood/lymphocytes as compared to unexposed controls (Jarvholm et al, 1999).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) PAHs have been determined in the blood and tissues of experimental animals. Direct biologic measurement of PAHs currently is not clinically useful or cost-effective. Indirect methods of determining exposure are available but have not yet proven clinically useful (ATSDR, 1990).
    B) Acute respiratory effects in persons at PAH-containing workplaces are typically due to other toxic agents at the worksite (ATSDR, 1990). Arterial blood gases, chest x-ray, and other monitoring may be indicated, based on the patient's presentation and the exposure characteristics.
    C) Chronic effects, particularly cancer, are more common than acute toxicity. Routine monitoring and physical assessments (e.g, complete blood count, hepatic and renal function tests, chest xray and pulmonary function tests, dermal assessments) of individuals with significant exposure is recommended, even in the absence of symptoms (ATSDR, 1990).
    4.1.2) SERUM/BLOOD
    A) TOXICITY
    1) Chronic effects involving the hematopoietic system, lungs, skin, oral cavity, liver, kidneys, and possibly gastrointestinal tract are more common than acute effects. Monitoring principally addresses effects of chronic exposure.
    B) HEMATOLOGIC
    1) These agents may produce abnormalities of the hematopoietic system. Monitoring the complete blood count is suggested for patients with significant exposure to screen for evidence of leukemia or aplastic anemia.
    C) BLOOD/SERUM CHEMISTRY
    1) These agents may produce hepatotoxicity (based on animal studies) and/or renal toxicity. Monitoring of liver function tests and renal function tests is suggested for patients with significant exposure.
    D) ACID/BASE
    1) Exposure to PNAs may also involve exposure to other substances which produce acute respiratory effects (ATSDR, 1990) are present, it may be useful to monitor arterial blood gases.
    4.1.3) URINE
    A) URINALYSIS
    1) These agents may produce nephrotoxicity, usually after chronic exposure. Monitoring of urinalysis is suggested for patient with significant exposure.
    2) NIOSH/OSHA RECOMMENDATIONS - At a minimum, determine the specific gravity, and presence of albumin or glucose; obtain a centrifuged microscopic examination of the sediment, and check for the presence of red blood cells.
    B) OTHER
    1) In workers with 5 or more years of exposure or who are 45 years of age or greater, obtain a urine cytology examination (Mackinson et al, 1981; (HSDB , 1993).
    4.1.4) OTHER
    A) OTHER
    1) MONITORING
    a) Workers chronically exposed to PAHs should have periodic chest x-rays and pulmonary function tests (ATSDR, 1993).
    b) NIOSH/OSHA RECOMMENDATIONS (HSDB , 1993) Mackinson et al, 1981) - Oral cavity, respiratory tract, bladder, and kidney examinations.
    1) Examine the skin for evidence of CHRONIC DISORDERS, PREMALIGNANT OR MALIGNANT LESIONS, HYPERPIGMENTATION, or PHOTOSENSITIVITY.
    2) SPUTUM CYTOLOGY - In workers with 10 or more years of exposure, obtain a SPUTUM CYTOLOGY EXAMINATION.
    3) CHEST X-RAY - Periodic chest x-rays are indicated for chronically exposed workers.
    4) These agents may produce abnormalities of the hematopoietic system. Monitoring the complete blood count is suggested for patients with significant exposure to screen for evidence of leukemia or aplastic anemia.
    5) At a minimum, determine the specific gravity, and presence of albumin or glucose; obtain a centrifuged microscopic examination of the sediment, and check for the presence of red blood cells.
    c) FREQUENCY - ANNUALLY for workers less than 45 years of age or with less than 10 years exposure to coal tar volatiles;
    1) SEMIANNUALLY for workers 45 years of age or greater, or with 10 or more years of coal tar volatiles exposure.
    d) Exfoliated buccal cells can be used for monitoring potential genetic damage in humans occupationally exposed to PAHs (Karahalil et al, 1999).

Radiographic Studies

    A) CHEST RADIOGRAPH
    1) Exposure to PAHs may be complicated by exposure to other substances which produce acute respiratory effects (ATSDR, 1990). If respiratory tract irritation is present, monitor chest xray.

Methods

    A) MULTIPLE ANALYTICAL METHODS
    1) Measurement of PAHs, PAH metabolites, and PAH metabolite DNA adducts in the blood or tissues of experimental animals has been conducted (ATSDR, 1990; Amin et al, 1993; Ronai et al, 1994).
    2) Proton Nuclear Magnetic Resonance (NMR) and gas chromatography/mass spectrometry (GC/MS) can be used to identify PAHs in complex mixtures (Lee et al, 1976).
    3) A fluorescent method for detecting benzo(a)pyrene diolepoxide-DNA adducts in peripheral lymphocytes has a lower detection limit of 1 adduct per 10(8) nucleotides. The results correlated well with those obtained from P-32 postlabeling analysis and ELISA assays (Rojas et al, 1994).
    4) A monoclonal antibody has been isolated which reacts with DNA adducts of benzo(a)pyrene, benz(a)anthracene, chrysene, dibenz(a,h)anthracene, and picene. It also recognizes protein adducts of benzo(a)pyrene, benz(a)anthracene, and chrysene. This tool shows promise for biological monitoring of exposure to these PAH's (Booth et al, 1994).
    5) An ELISA has been used to determine antibodies to PNAs-DNA adducts using in the sera of coke oven workers (Harris et al, 1986).
    6) Urinary levels of the PAH metabolite, 1-hydroxypyrene can be quantitated using HPLC (Omland et al, 1994), and have coorelated with PAH exposure in workers (Ferreira et al, 1994; Hansen et al, 1994; Ovrebo et al, 1994; Elovaara et al, 1995; Heikkila et al, 1995; Vanschooten et al, 1995).
    7) PAH metabolite adducts of human hemoglobin generated in vitro have been measured by modified gas chromatography-mass spectrometry (Taghizadeh & Skipper, 1994) and by fluorescence spectroscopy (ATSDR, 1990).
    8) Cells with high frequencies of chromosomal aberrations were a sensitive marker for persons exposed to PAH's in coke oven and graphite electrode plant work, compared with unexposed controls (Buchet et al, 1995).
    9) Ambient airborne levels of naphthalene and pyrene may be useful as measures of total exposure to carcinogenic PAHs (Hansen et al, 1991).
    10) An HPLC with fluorimetric detection and solid phase extraction technique can be used to measure PAHs in tea infusion samples (Kayali-Sayadi et al, 1998).
    B) OTHER
    1) LIMITATIONS -
    a) Biological monitoring techniques testing for the presence of metabolites in blood or urine, or DNA adducts in blood or tissues, are limited to identifying whether or not exposure has occurred, such as in epidemiological studies. They are not routinely recommended for clinical evaluation of patients, because neither normal background nor toxic levels have been established and the tests are costly (ATSDR, 1990; ATSDR, 1993).
    b) Other limitations include confounding variables (e.g, the use of drugs or cigarettes), individual variability of PAH metabolism, nonspecificity of some techniques, and the low-level nature of most human exposure (ATSDR, 1990).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) PAHs have been determined in the blood and tissues of experimental animals. Direct biologic measurement of PAHs currently is not clinically useful or cost-effective. Indirect methods of determining exposure are available but have not yet proven clinically useful (ATSDR, 1990).
    B) Acute respiratory effects in persons at PAH-containing workplaces are typically due to other toxic agents at the worksite (ATSDR, 1990). Arterial blood gases, chest x-ray, and other monitoring may be indicated, based on the patient's presentation and the exposure characteristics.
    C) Chronic effects, particularly cancer, are more common than acute toxicity. Routine monitoring and physical assessments (e.g, complete blood count, hepatic and renal function tests, chest xray and pulmonary function tests, dermal assessments) of individuals with significant exposure is recommended, even in the absence of symptoms (ATSDR, 1990).

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) Toxicity from these substances involves chronic exposure, toxicity after acute ingestions is unlikely and gastric decontamination is generally NOT indicated.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Toxicity from these substances involves chronic exposure, toxicity after acute ingestions is unlikely and gastric decontamination is generally NOT indicated. Consider activated charcoal in the unlikely event of large ingestion.
    B) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) Toxicity after acute ingestions is unlikely. Treatment is symptomatic and supportive.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.
    6.7.2) TREATMENT
    A) IRRITATION SYMPTOM
    1) If bronchospasm and wheezing occur, consider treatment with inhaled sympathomimetic agents.
    2) Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    3) Monitor arterial blood gases and/or pulse oximetry, pulmonary function tests, and chest x-ray in patients with significant exposure.
    B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    6.9.2) TREATMENT
    A) SKIN ABSORPTION
    1) Some chemicals can produce systemic poisoning by absorption through intact skin. Carefully observe patients with dermal exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    B) BURN
    1) APPLICATION
    a) These recommendations apply to patients with MINOR chemical burns (FIRST DEGREE; SECOND DEGREE: less than 15% body surface area in adults; less than 10% body surface area in children; THIRD DEGREE: less than 2% body surface area). Consultation with a clinician experienced in burn therapy or a burn unit should be obtained if larger area or more severe burns are present. Neutralizing agents should NOT be used.
    2) DEBRIDEMENT
    a) After initial flushing with large volumes of water to remove any residual chemical material, clean wounds with a mild disinfectant soap and water.
    b) DEVITALIZED SKIN: Loose, nonviable tissue should be removed by gentle cleansing with surgical soap or formal skin debridement (Moylan, 1980; Haynes, 1981). Intravenous analgesia may be required (Roberts, 1988).
    c) BLISTERS: Removal and debridement of closed blisters is controversial. Current consensus is that intact blisters prevent pain and dehydration, promote healing, and allow motion; therefore, blisters should be left intact until they rupture spontaneously or healing is well underway, unless they are extremely large or inhibit motion (Roberts, 1988; Carvajal & Stewart, 1987).
    3) TREATMENT
    a) TOPICAL ANTIBIOTICS: Prophylactic topical antibiotic therapy with silver sulfadiazine is recommended for all burns except superficial partial thickness (first-degree) burns (Roberts, 1988). For first-degree burns bacitracin may be used, but effectiveness is not documented (Roberts, 1988).
    b) SYSTEMIC ANTIBIOTICS: Systemic antibiotics are generally not indicated unless infection is present or the burn involves the hands, feet, or perineum.
    c) WOUND DRESSING:
    1) Depending on the site and area, the burn may be treated open (face, ears, or perineum) or covered with sterile nonstick porous gauze. The gauze dressing should be fluffy and thick enough to absorb all drainage.
    2) Alternatively, a petrolatum fine-mesh gauze dressing may be used alone on partial-thickness burns.
    d) DRESSING CHANGES:
    1) Daily dressing changes are indicated if a burn cream is used; changes every 3 to 4 days are adequate with a dry dressing.
    2) If dressing changes are to be done at home, the patient or caregiver should be instructed in proper techniques and given sufficient dressings and other necessary supplies.
    e) Analgesics such as acetaminophen with codeine may be used for pain relief if needed.
    4) TETANUS PROPHYLAXIS
    a) The patient's tetanus immunization status should be determined. Tetanus toxoid 0.5 milliliter intramuscularly or other indicated tetanus prophylaxis should be administered if required.
    C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Range Of Toxicity

Summary

    A) The minimum lethal human dose to this agent has not been delineated.
    B) The maximum tolerated human exposure to this agent has not been delineated.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) The maximum tolerated human exposure to this agent has not been delineated.

Maximum Tolerated Exposure

    A) ROUTE OF EXPOSURE
    1) CIGARETTE SMOKE - One cigarette may yield 10 to 50 nanograms of benzo(a)pyrene, 18 nanograms of chrysene, 40 nanograms of dibenz(a,h)anthracene, and 12 to 140 nanograms of benz(a)anthracene (ATSDR, 1993).
    a) Cigarette smoke (direct and sidestream) is the overall major source of nonoccupational exposure to PAHs for the general public (Holbrook, 1990).
    b) One-pack-per-day cigarette smokers inhale between 0.4 microgram per day (filtered cigarettes) and 0.7 microgram per day (unfiltered cigarettes) of benzo(a)pyrene (Holbrook, 1990).
    c) For comparison, the average exposure to PAHs from ambient air is 0.02 micrograms/day (Holbrook, 1990).
    2) PASSIVE SMOKERS - can also inhale appreciable amounts of PAH-containing sidestream smoke in an indoor environment (Holbrook, 1990).
    3) SOIL NEAR OIL REFINERIES - May contain levels of PAHs as high as 200 nanograms per kilogram of dried soil (ATSDR, 1993)
    a) Soil from cities and areas with heavy automobile traffic may contain PAH levels tenfold higher (ATSDR, 1993).
    4) CITIES WITH COKE OVENS - Airborne concentrations of PAHs in cities with coke ovens may reach 150 nanograms/m(3) (compared to an OSHA PEL workplace limit of 150,000 nanograms/m(3)) (ATSDR, 1993).
    a) The greatest environmental PAH exposures to the general public result from refuse burning, power and heat generation, and coke production (Holbrook, 1990).
    5) AUTOMOBILE EXHAUST - Automobile exhaust is responsible for only a small percentage of ambient air PAH exposure (generally about 1%) (Holbrook, 1990).
    a) Benzo(a)pyrene typically makes up only 3% to 5% of the total amount of PAHs generated in motor vehicle exhaust (Holbrook, 1990).
    6) FOODS - PAHs can be found in foodstuffs due to biosynthesis, adsorption of particulates deposited on leafy surfaces from atmospheric sources, and processing or cooking of foods before they are consumed (Pike, 1992).
    a) SMOKED FISH - May contain up to 2.0 micrograms/kilogram of benzo(a)pyrene (ATSDR, 1993).
    b) OTHER - PAHs have been found in foods, including broiled meat and fish, cereals, refined oils and fats, roasted coffee, salad, smoked meat or fish, spinach, and tea.
    7) PLANTS -
    a) Plant surfaces have higher concentrations than internal parts. Above ground plants have higher concentrations than below ground plants.
    b) Broad-leaf plants have higher concentrations than thin-leaf plants; WASHING is NOT an effective method of removing PAH contamination.
    c) Some terrestrial plants can internalize PAHs by translocation through roots or leaves. Certain plants can also SYNTHESIZE PAHs.

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) GENERAL
    a) Have not been etablished for acute exposure to individual PAH compounds.

Pharmacology Toxicology

Toxicologic Mechanism

    A) CARCINOGENICITY -
    1) The first occupational cancer described was that of scrotal cancer in chimney sweeps exposed to PAHs in soot and ash by Dr Percival Pott in 1775 (ATSDR, 1993; Ellenhorn & Barceloux, 1988).
    2) Coal tar related-cancer has since been studied in both humans and experimental animals (ATSDR, 1993).
    3) Benzo(a)pyrene, first isolated from coal tar in the 1930s, is carcinogenic when applied to the skin of experimental animals (ATSDR, 1993; Ellenhorn & Barceloux, 1988).
    a) Hundreds of other PAHs have also been described, and many of them (but NOT ALL) are carcinogenic in experimental animals (ATSDR, 1993).
    b) Anthracene and phenanthrene are generally considered NOT to be carcinogenic (Ellenhorn & Barceloux, 1988).
    B) CARCINOGENIC MECHANISMS -
    1) PAH-related carcinogenesis may result if a PAH-DNA adduct forms in a site critical to DNA regulation of cell growth or differentiation (ATSDR, 1993). For certain PAHs, the extent of DNA binding is correlated with carcinogenic potential, although metabolism of these compounds may be necessary for them to react with cellular constituents (Brookes & Lawley, 1964; Amin et al, 1993).
    a) If repair does not occur, a mutation may occur during cellular replication (ATSDR, 1993). Cells with rapid replicative turnover (ie, bone marrow, skin, gastrointestinal mucosa, lung) may be more susceptible (ATSDR, 1993; Pike, 1992).
    2) The "bay region" theory suggests that an epoxide PAH metabolite will be highly reactive in forming DNA adducts if the epoxide is located in the "bay region" of the PAH molecule (ie, the epoxide is on a ring joined to the rest of the condensed ring structure by two carbons) (Ellenhorn & Barceloux, 1988; Holbrook, 1990; Pike, 1992; Amin et al, 1993; ATSDR, 1993).
    3) It has been hypothesized that mutations result from direct binding of the bay region of PAH diol-epoxide metabolites to the Ha-ras oncogene. Activated Ha-ras oncogenes with mutations in codons 12, 13, or 61 have been found in studies of mouse skin tumors induced by PNAs (Ronai et al, 1994).
    a) Studies by Ronai et al (1994) of tumors induced by a benzo[c]phenanthrene diol-epoxide metabolite (anti-benzo[c]phenanthrene-3,4-diol-1,2-epoxide) found numerous Ha-ras gene mutations in codon 61 of mouse skin tumors. These studies suggest that the mechanism of benzo[c]phenanthrene-induced skin tumors is Ha-ras gene mutations produced by the diol-epoxide metabolite.
    4) The K-region is the most active site on the prototype benzo(a)pyrene molecule and its corresponding cytochrome P-450 oxidase epoxide metabolite (Holbrook, 1990; Ellenhorn & Barceloux, 1988).
    a) The ultimate carcinogen of cytochrome P-450 oxidase metabolism of benzo(a)pyrene is 7,8-dihydro-7,8-diol-9,10-epoxide (Holbrook, 1990; Pike, 1992).
    5) Considerations of molecular structure may be used to predict the carcinogenic potential of PAH compounds (Flesher & Myers, 1991).
    6) Benz(a)anthracene (the model carcinogenic PAH) undergoes bioalkalytion and biooxidation reactions in experimental animals; these reactions are NOT noted with NONCARCINOGENIC PAHs (Flesher & Myers, 1990).
    7) DIESEL EXHAUST - The carcinogenicity of diesel exhaust may be due to the presence of PAH compounds with four or more benzene rings (Grimmer et al, 1987).
    C) ANTIESTROGENICITY
    1) Certain PAH fractions from environmental samples have been shown to have antiestrogenic activity in human breast cancer cells in vitro (Arcaro et al, 1999).
    D) OXIDATIVE METABOLISM
    1) Genotoxic effects of nitro-PAHs in human cells in vitro may require oxidative metabolism (Grosovsky et al, 1999).
    E) ADDITIVE ANTICHOLINESTERASE ACTIVITY
    1) In vitro, certain PAHs have an additive anticholinesterase effect with chlorpyrifos (Jett et al, 1999).

Physicochemical

Physical Characteristics

    A) PAHs are low volatility solids at room temperature (ATSDR, 1993).

Molecular Weight

    A) Varies

References

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