GAS/PARTICLE AND SIZE DISTRIBUTIONS OF POLYCYCLIC AROMATIC HYDROCARBONS IN AMBIENT AIR IN TOKYO 2001–2002

By using an Andersen sampler equipped with a low-pressure impactor, samples of 12 size-classified (>0.13 μm to <12 μm) airborne particles and samples of gaseous components were taken from the air in Tokyo for continuous periods of 19 weeks in the summer of 2001 and 17 weeks in the winter of 2001–2. The sampling filters were changed weekly. The concentrations of eight polycyclic aromatic hydrocarbons (PAHs) in the particulate and gas-phase samples were measured by reverse-phase high performance liquid chromatography (HPLC) with fluorescence detection. Pyrene was detected in the gas phase in both summer and winter: 59% of the total pyrene detected was present in the gas phase in summer, but this fraction decreased to 40% in winter. In the particle fractions, the summer levels of benzo[k]fluoranthene (BkF), dibenz[a,h]anthracene (dBahA), and benzo[a]anthracene (BaA) peaked in particles of diameter 1.25 μm, and benzo[ghi]perylene (BghiP), benzo[a]pyrene, benzo[b]chrysene (BbC), and dibenzo[a,e]pyrene (dBaeP) peaked in particles of diameter 0.76 μm. In winter, BkF, BghiP, BaA, BbC, and dBaeP levels peaked in particles of diameter 0.52 μm, whereas dBahA peaked in particles of diameter 0.76 μm.     

SYNTHESES OF ADDUCTS OF ACTIVE METABOLITES OF CARCINOGENIC POLYCYCLIC AROMATIC HYDROCARBONS WITH 2′-DEOXYRIBONUCLEOSIDES

Syntheses are reported for: (1 Harvey, R. G. 1991. Polycyclic Aromatic Hydrocarbons: Chemistry and Carcinogenicity, Cambridge, , U.K.: Cambridge University Press.  [Google Scholar]) adducts of the quinone metabolites of benzo[a]pyrene (BPQ) and benz[a]anthracene (BAQ) with 2′-deoxyadenosine and 2′-deoxyguanosine; (2 Conney, A. H. 1982. Induction of Microsomal Enzymes by Foreign Chemicals and Carcinogenesis by Polycyclic Aromatic Hydrocarbons. Cancer Res., 42: 4875–4917. [PUBMED][INFOTRIEVE][CSA][PubMed], [Web of Science ®] , [Google Scholar]) ¹⁵ N-labelled analogs of these adducts (four or five nitrogen atoms ¹⁵ N-labelled); (3 Dipple, A. 1994. “Reactions of Polycyclic Aromatic Hydrocarbons with DNA”. In DNA Adducts: Identification and Biological Significance, Edited by: Hemminki, K., Dipple, A., Segerbäck, D., Kadulbar, F. F., Shuker, D. and Bartsch, H. pp. 107–129. IARC Scientific Publication No. 125.  [Google Scholar]) depurinated adducts of BPQ and BAQ with adenine or guanine covalently linked to the N7 or N9 positions of the purine bases; (4 Jeffrey, A. M., Weinstein, I. B., Jennette, K., Grzeskowiak, K., Nakanishi, K., Harvey, R. G., Autrup, H. and Harris, C. 1977. Structures of Benzo[a]pyrene-Nucleic Acid Adducts Formed in Human and Bovine Bronchial Explants. Nature (London)., 269: 348–350. [CSA][CROSSREF][Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) ¹³ C-labelled derivatives of benzo[a]pyrene, BPQ, benzo[a]pyrene trans-7,8-dihydrodiol, and the benzo[a]pyrene anti-diol epoxide (with ¹³ C-atoms at the 5- and 11-positions); and (5 Jennette, K., Jeffrey, A. M., Blobstein, S. H., Beland, F. A., Harvey, R. G. and Weinstein, I. B. 1977. Characterization of Nucleoside Adducts from the in Vitro Reaction of Benzo[a]pyrene-7,8-dihydrodiol-9,10-oxide or Benzo[a]pyrene-4,5-oxide with Nucleic Acids. Biochemistry, 16: 932–938. [PUBMED][INFOTRIEVE][CSA][CROSSREF][Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) depurinated adducts formed by reactions of the benzo[a]pyrene radical-cation at the C ⁸ -, N ⁷ -, and N ⁹ -positions of adenine and guanine.     

PARTITIONING OF π-ELECTRONS IN RINGS OF POLYCYCLIC conjugated HYDROCARBONS. PART 1: CATACONDENSED BENZENOIDS

Recently a novel view on Kekulé valence structures (or resonance structures) was reported in which their standard geometrical representation was replaced by a numerical representation obtained by assigning π-electrons associated with CC double bonds to individual benzenoid rings. In the present article, we examine in more detail the partitioning of π-electrons to benzenoid rings for cata-condensed benzenoid hydrocarbons. For special families of cata-condensed benzenoids, we offer formulas which allow one to obtain the average π-electron ring content for individual benzenoid rings of polycyclic conjugated hydrocarbons. We also show that the average π-electron ring content for individual benzenoid rings can be calculated from Pauling bond orders without a need to examine all Kekulé resonance structures of a molecule.     

THE SIGNIFICANCE OF POLYCYCLIC AROMATIC HYDROCARBONS AS ENVIRONMENTAL CARCINOGENS. 35 YEARS RESEARCH ON PAH—A RETROSPECTIVE

In vivo studies with laboratory animals as well as in vitro studies with bacteria and mammalian cell cultures have demonstrated that the mutagenic and/or carcinogenic properties of numerous PAHs require metabolic transformation. Metabolism of PAHs has been explored in vitro using cellular microsomal fractions, mammalian cell cultures and later genetically engineered cells expressing cytochromes P450 from several species including humans.

Balancing the carcinogenic potential of some environmental matrices (vehicle exhaust, condensate of hard coal combustion effluents, cigarette smoke condensate, used motor oil) after separation into sub-fractions evidenced that the carcinogenic effect may be attributed almost exclusively to PAH. Mixtures of well-known carcinogenic PAH in concentrations as present in these matrices, however, did not explain the total biological effect. Thus, it had been speculated that either very potent unknown carcinogens are still hidden in the PAH fraction, or that synergistic effects (enzyme induction) play a significant role.

In parallel to these carcinogenicity studies, the metabolism of various PAHs has been investigated in rat liver microsomes from untreated animals as well as from animals pre-treated with inducers of cytochrome P450. It was found that even non-carcinogenic PAHs possess a significant inducing potential. Moreover, in several mammals a highly species-specific metabolism of PAH could be observed allowing a critical view to the extrapolation from animal experiments to the human situation. This was further confirmed by experiments with mammalian cell cultures including human ones as well as by metabolic studies with genetically engineered Chinese hamster V79 cells singularly expressing various cytochrome P450 enzymes from a number of different species (human, rat, mouse, fish). With these cell lines metabolic studies were carried out with a larger number of PAHs as substrates including phenanthrene, pyrene, chrysene, benzo[a]anthracene, benzo[c]phenanthrene, benzo[a]pyrene, dibenzo[a,l]pyrene, and benzo[c]chrysene.

Based on the metabolism results, analytical methods have been developed to determine urinary biomarkers of human PAH exposure. Human biomonitoring studies have been performed with different occupationally exposed individuals as well as within smokers and non-smokers of the general population. Endogenous PAH exposure levels and changes in the urinary excreted metabolic profile depending on exposure level have been determined.     

USE OF THE AEROSIZER® AERODYNAMIC PARTICLE SIZE ANALYZER TO CHARACTERIZE AEROSOLS FROM PRESSURIZED METERED-DOSE INHALERS (pMDIs) FOR MEDICATION DELIVERY

The Aerosizer^® aerodynamic particle size analyzer is widely used for the rapid assessment of medical aerosols. Its real-time capability to make measurements offers a significant advantage in terms of user convenience compared with aerodynamic particle size analysis by cascade impactor or multi-stage liquid impinger. However, the present study has highlighted a limitation in its use in the measurement of aerosols from many types of pressurized metered-dose inhaler (pMDI) in which the measured total number concentration exceeds about 10¹⁰ particles m^-3. The causes are complex, but appear primarily to be associated with the loss of electrical signals from individual particle-detection beam interactions, associated with timer insensitivity of the signal correlation system. This phenomenon occurs where several particles are present simultaneously within the measurement zone. Subsequent processing of the time-of-flight data may result in significant distortion of the reported size distribution, including in extreme cases the absence of portions of the data where the AUTOCOMBINE feature is used to create the full size distribution from the low and high detection sensitivity sub-ranges.