Occupational Exposure to Polycyclic Aromatic Hydrocarbons and Elevated Cancer Incidence in Firefighters.

Cancer incidence appears to be higher amongst firefighters compared to the general population. Given that many cancers have an environmental component, their occupational exposure to products of carbon combustion such as polycyclic aromatic hydrocarbons (PAHs) is of concern. This is the first UK study identifying firefighters exposure to PAH carcinogens. Wipe samples were collected from skin (jaw, neck, hands), personal protective equipment of firefighters, and work environment (offices, fire stations and engines) in two UK Fire and Rescue Service Stations. Levels of 16 US Environmental Protection Agency (EPA) PAHs were quantified together with more potent carcinogens: 7,12-dimethylbenzo[a]anthracene, and 3-methylcholanthrene (3-MCA) (12 months post-initial testing). Cancer slope factors, used to estimate cancer risk, indicate a markedly elevated risk. PAH carcinogens including benzo[a]pyrene (B[a]P), 3-MCA, and 7,12-dimethylbenz[a]anthracene PAHs were determined on body surfaces (e.g., hands, throat), on PPE including helmets and clothing, and on work surfaces. The main exposure route would appear to be via skin absorption. These results suggest an urgent need to monitor exposures to firefighters in their occupational setting and conduct long-term follow-up regarding their health status.

1-Hydroxy- and 2-hydroxy-3-methylcholanthrene: regioselective and stereoselective formations in the metabolism of 3-methylcholanthrene and enantioselective disposition in rat liver microsomes.

Absolute configurations of enantiomeric 1-hydroxy-3-methylcholanthrene (1-OH-3MC) and 2-hydroxy-3-methyl-cholanthrene (2-OH-3MC) were determined by the exciton chirality circular dichroism (CD) method as their p-nitrobenzoate derivatives. Enantiomers of 1-OH-3MC were resolved by HPLC using a column packed with chiral stationary phase (CSP) (R)-N-(3,5-dinitrobenzoyl)phenylglycine covalently bonded to gamma-aminopropylsilanized silica. Enantiomers of 2-OH-3MC were resolved as diastereomeric (-)-methoxyacetates by normal-phase HPLC. 1-OH-3MC and 2-OH-3MC, formed in the metabolism of 3MC by liver microsomes from untreated, phenobarbital (PB)-treated and 3MC-treated male Sprague-Dawley rats, were first isolated as a mixture by reversed-phase HPLC and subsequently separated by normal-phase HPLC. Concentration ratios of [1-OH-3MC]:[2-OH-3MC] formed in the metabolism of 3MC by three rat liver microsomal preparations (at 0.5 mg protein per ml of incubation mixture and an incubation time of 10 min) were found to be: 30:70 (control), 21:79 (PB treated) and 10:90 (3MC treated) respectively. R/S enantiomer ratios of 1-OH-3MC formed in the metabolism of 3MC by three rat liver microsomal preparations were determined by CSP HPLC: 35:65 (control), 39:61 (PB treated) and 46:54 (3MC treated) respectively. R/S enantiomer ratios of 2-OH-3MC formed in the metabolism of 3MC by three rat liver microsomal preparations were determined by CD spectral data: 14:86 (control), 6:94 (PB treated) and 6:94 (3MC treated) respectively. Metabolism of racemic 1-OH-3MC and 2-OH-3MC by all three rat liver microsomal preparations was found to be substrate enantioselective; the rate of 1S-OH-3MC metabolism was faster than that of 1R-OH-3MC, whereas the rate of 2R-OH-3MC metabolism was faster than that of 2S-OH-3MC.

9,10-Dihydroxy-9,10-dihydro-3-methylcholanthrene-2-one: a principal metabolite of the potent carcinogen 3-methylcholanthrene-2-one by rat liver microsomes.

A principal metabolite, formed in the metabolism of the potent carcinogen 3-methylcholanthrene-2-one (3MC-2-one) by liver microsomes from either untreated, or phenobarbital-treated or 3-methylcholanthrene (3MC)-treated rats, was isolated by reversed-phase HPLC. This metabolite has been identified as a 9,10-dihydrodiol with a (9R,10R):(9S,10S) enantiomer ratio of approximately 84:16 by all three rat liver microsomal preparations. The 9,10-dihydrodiol metabolite and its NaBH4 reduction products [a pair of diastereomeric 9,10-dihydroxy-9, 10-dihydro-2-OH-3MC (2-OH-3MC 9,10-dihydrodiols)] were characterized by UV-visible absorption, mass, and circular dichroic spectral, and chiral stationary phase HPLC analyses. Identification of 9,10-dihydroxy-9,10-dihydro-3MC-2-one (3MC-2-one 9,10-dihydrodiol) as the predominant metabolite of the potent carcinogen 3MC-2-one suggests that 3MC-2-one may be metabolically activated to a bay region 9,10-diol-7,8-epoxide, similar to the previously established metabolic activation pathways of 3MC and 1-hydroxy-3-methylcholanthrene (1-OH-3MC).

Separation and identification of 3-methylcholanthrene-related compounds by gas chromatography-mass spectrometry.

Separation and identification of 3-methylcholanthrene and its synthesized derivatives were examined by gas chromatography-mass spectrometry (GC-MS) system. Hydroxyl derivatives were silylated and all chemicals were applied to columns of OV-1 and Dexsil-300 at a constant temperature of 260 degrees and 290 degrees, respectively. Mass spectra of all derivatives were simple at ionization voltage of 20 eV and their molecular ions gave base peaks in most cases. Mass fragmentography plotted against molecular ions satisfactorily separated all standard derivatives so far examined.

Chromatographic separation of autofluorescent and quenching substances from the hydrocarbon in tissue.

In spite of the recent progress in fluorometry, the measurement of carcinogenic hydrocarbons in tissue has been carried out with insufficient accuracy because of the presence of substances in the tissue interfering with fluorometry. Such substances, autofluorescent and quenching substances, were removed from ethanol extracts of the tissue by Sephadex LH-20 column chromatography. By elution of the column with ethanol, the interfering substances appeared in fractions of the void volume for 3-methylcholanthrene chromatography. In addition, the excitation wavelength for autofluorescent substances was found to be far from that for 3-methylcholanthrene, for which the excitation was at 300 nm and the luminescence was measured at 400 nm. Chromatographic separation of 3-methylcholanthrene and its metabolites in the bile and veces obtained from rats was done and only one peak consisting of conjugated metabolites was found on the chromatogram of the bile, though three peaks consisting respectively of the parent hydrocarbon with some metabolites, nonconjugated metabolites, and conjugated metabolites were observed in the feces. Total amounts of 3-methylcholanthrene and its metabolites, though the majority of the fluorescent substances were the parent hydrocarbon, in the lung and other organs were measured at various intervals after an intrabronchial application of 1 or 5 mg of 3-methylcholanthrene in Freund's incomplete adjuvant to rats. Preservation of the hydrocarbons in the treated lung was confirmed and this was considered to take part in the enhanced occurrence of epidermoid tumors in the lung.