Search

Historically, exposure to complex mixtures such as soot, coal tar, mineral oils, and cigarette smoke has been associated with increased cancer mortality. Benzo[a]pyrene (BaP) has been used to predict the carcinogenic potency of mixtures. Two complete carcinogenicity C3H/HEJ mouse skin bioassays were undertaken to determine the effect of low doses of BaP on the carcinogenic potential of mixtures. A toluene solution containing 0.1% each of five noncarcinogenic polycyclic aromatic hydrocarbons (PAHs), anthracene, chrysene, pyrene, fluoroanthene, and phenanthrene, produced tumors in 23% of the mice with a latent period of 73 weeks. With the addition of a 0.001% BaP to the above solution, 47% of the mice produced tumors with a latent period of 66 weeks. In the second study, coal tar in toluene, which was determined to contain 0.0006% BaP, produced tumors in 51% of mice with a latent period of 73 weeks. In both studies the BaP solutions by themselves did not produce tumors. In a third study, the 9-, 2-, and 3-methylbenz[a]-anthracene compounds were noncarcinogenic using toluene as the solvent. With the substitution of n-dodecane for toluene all three compounds produced significant numbers of tumors. The results indicate that (1) low dose levels of BaP can have an impact on the carcinogenic potential of mixtures, (2) the presence or absence of BaP is not always sufficient to account for the observed potency and the synergistic effects of other substances which might be present, and (3) that certain noncarcinogenic methylbenz[a]anthracenes can have their carcinogenic potential altered by a change in the solvent used.

The conversion or processing of shale, coal, or petroleum involves elevated temperatures and altered pressures, and under these conditions polynuclear aromatic hydrocarbons are likely to form. Certain compounds of this type exhibit carcinogenic activity for a variety of organ sites in experimental animals and epidemiological evidence strongly implicates their role as carcinogens in man. It is then not unexpected that many liquid fractions derived from shale and coal are carcinogenic when subjected to bioassay. Benzo(a)pyrene, [B(a)P], is frequently considered to be an indicator substance. It is clear that when a small quantity of B(a)P is present in a fraction, the fraction will exhibit carcinogenic activity in a bioassay (mouse skin). However, it does not follow that the lack of detectable B(a)P insures that the fraction will be noncarcinogenic. Several fractions have been analyzed for their content of B(a)P and then subjected to bioassay. A method for testing complex mixtures for their carcinogenic potential is described. The carcinogenic potency of these fractions are compared to petroleum fractions.

Benzo[a]pyrene (BaP), a ubiquitous potent carcinogen, has been associated with the increased incidence of human bronchiogenic carcinoma in occupational and urban settings. A detailed knowledge of the rate and pattern of metabolite formation and factors affecting their formation is essential for understanding the mechanism of action of BaP in the lung. An isolated perfused New Zealand rabbit lung preparation was used to investigate the effects of a crude airborne particulate mixture on the metabolism of BaP. [14C]BaP with and without crude air particulate (CAP) was administered intratracheally to an isolated perfused lung (IPL) preparation after intratracheal pretreatment of the whole animal with CAP and/or BaP, or intraperitoneal pretreatment of the whole animal with BaP. BaP and its metabolites were extracted from perfusing blood at 6 time points up to 180 min after administration of [14C]BaP to the IPL. BaP and its metabolites were also extracted from lung tissue, washout fluid, aveolar macrophages, and trachea bronchi at the end of the perfusion at 180 min. Patterns of BaP metabolites were determined by chromatographic techniques and liquid scintillation counting. Particulate pretreatment of the whole animal or administration of the particulate to the IPL altered BaP metabolism by the perfusing lung. Particulate pretreatment of the whole animal resulted in increases in the total rates of appearance of metabolites of BaP in the blood (ng/g lung . h), while particulate administration to the IPL resulted in decreases in the total rate of appearance of metabolites of BaP in the blood and negated the effects of pretreatments. Coadministration of particulate with BaP to the IPL with and without particulate pretreatment of the whole animal, or BaP administration to the IPL preceded by particulate pretreatment of the whole animal, enhanced dihydrodiol formation and depressed formation of water-soluble materials. This is important because dihydrodiol formation is considered part of the active pathway of BaP carcinogenicity. These data suggest that pulmonary particulate exposure in the presence of BaP results in the initial increased production of dihydrodiols of BaP that may be further metabolized to compounds believed to be the ultimate carcinogenic form(s) of BaP.

The carcinogenic potentials of certain present day roofing materials and dust produced during the removal of an old coal tar pitch roof were evaluated using a mouse skin bioassay. Traditional coal tar pitch and dust from removal of an old roof were significantly more carcinogenic than coal derived roofing bitumen, but all were strongly carcinogenic. The benzo(a)pyrene concentration of these materials ranged from 0.064 to 0.08%, but each was significantly more carcinogenic than 0.1% benzo(a)pyrene alone. No tumors were produced by the application of petroleum derived roofing asphalt.