Benzo(j)fluoranthene
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Preferred IUPAC name
Benzo[j]fluoranthene | |
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3D model (
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100.005.374 |
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RTECS number
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UNII | |
UN number | 3077 |
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Properties | |
C20H12 | |
Molar mass | 252.3093 |
Appearance | solid |
Density | 1.286 g/cm3 |
Melting point | 165 °C (329 °F; 438 K) |
Hazards | |
Flash point | 228.6 °C (443.5 °F; 501.8 K) |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Benzo[j]fluoranthene (BjF) is an
Structure and synthesis
BjF consists of two naphthalene-like structures which are fused by a cyclopentane structure. This cyclopentane is not included in the aromaticity of the molecule. BjF can be obtained when either 2-(1-chloroethenyl)benzo[c]phenanthrene or 6-(1-chloroethenyl)chrysene is treated by flash vacuum thermolysis (FVT) at high temperatures (above 900 °C) followed by ring rearrangements (ring contraction/expansion) to selectively yield BjF.[3] Benzo[k]fluoranthene may also be converted via similar processes to BjF by FVT at temperatures of at least 1100 °C (6% yield) or at least 1200 °C (11% yield) with 38% mass recovery.[4]
Reactivity
BjF can be functionalized by means of electrophilic aromatic substitution. In the body it is metabolized into phenols (3,4,6 or 10 hydroxy), dihydrodiols (4,5 and 9,10) and 4,5-dione[5] (fig. 1).
Mechanism of action
BjF is categorized by the IARC as possibly carcinogenic to human beings, like many other PAHs, on the basis of sufficient evidence in animals.[6] For example, BjF is active as a tumor initiator on mouse skin and is carcinogenic in both mouse skin and in rat lungs. Recently, BjF was also found to induce tumors in newborn mouse lung and liver.[7] The mechanism of actions of BjF is similar to other PAHs. The diolepoxide mechanism involves formation of stable and unstable DNA adducts, mainly at G and A, which can lead to mutations in proto-oncogenes (RAS) and tumour-suppressor genes (P53). Many polycyclic aromatic hydrocarbon diolepoxides and their precursor diols and epoxides are tumorigenic in animals. The radical cation mechanism involves generation of unstable adducts at G and A, leading to apurinic sites and mutations in HRAS. Orthoquinone formation could lead to stable and unstable DNA adducts and generation of reactive oxygen species, inducing mutations in P53.[8]
Toxicity
PAHs
One of the earliest connection between PAHs, combustion, and cancer was established by Cook and co-workers with the isolation of the carcinogen benzo[a]pyrene from coal tar extract.[9] Benzo[a]pyrene now has been well characterized in toxicology reports and is a known potent carcinogen.[10] Benzo[a]pyrene requires metabolic activation to become, ultimately, BPDE ((±)-anti-7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene) which binds to the DNA to form a covalent trans adducts at the N2 position of guanine.[11] Hereafter binding to DNA at cancer hotspots, especially in the P53 tumour suppressor gene at codons: 157, 248 and 273 (figure 3), it has the possibility of inducing lung cancer.[12] Structural similarity of PAHs contributes to the similarity in metabolism, biotransformation and toxicology. Benzo[a]pyrene has been extensively reviewed and is used as a model for the toxicology and metabolism of other PAHs.[13]
Benzo[j]fluoranthene
Specific studies on BjF showed that it exhibits mutagenic toxicity in S. typhimurium TA98 and TA1000 under the presence of microsomal activation.[14] BjF can form DNA-adducts, covalently binding of chemicals to DNA can result in strand breaks and DNA damage, which ultimately leads to mutations.[15] In mice studies BjF induced tumorigenic activity on the skin, lung adenomas and liver adenomas/hepatomas.[16][17][18][19] Lung implantation of BjF also induced lung epidermoid carcinomas in 3-month-old female rats.[20] Tail vein injection of BjF also causes covalently binding to mouse hemoglobin and serum proteins, with binding to serum proteins being 10-fold higher than to hemoglobin.[21]
References
- ^ Author unknown (23 June 2005) "Benzo[j]fluoranthene". TOXNET http://toxnet.nlm.nih.gov/cgi-bin/sis/search2/f?./temp/~ZHcJmU:1 (last consulted on: 19 March 2015)
- ^ Author unknown (date unknown) "Benzo[j]fluoranthene" Sigma-Aldrich [1] (last consulted on: 19 March 2015)
- ^ M. Sarobe et al. (1 January 1997) "High temperature gas phase syntheses of C20H12 cyclopenta-fused polycyclic aromatic hydrocarbons: benz[l]acephenanthrylene and benz[j]acephenanthrylene and their selective rearrangement to benzo[j]fluoranthene" Journal of the Chemical Society, Perkin Trans. 2
- ^ M. Sarobe et al. (1999) "Flash Vacuum Thermolysis of Acenaphtho[1,2-α]acenaphthylene, Fluoranthene, Benzo[k]- and Benzo[j]fluoranthene 2 Homolytic Scission of Carbon2Carbon Single Bonds of Internally Fused Cyclopenta Moieties at T ≥ 1100°C" European Journal of Organic Chemistry
- ^ E.H. Weyand et al. (1993) "Detection of the Major DNA Adducts of Benzo[j]fluoranthene in Mouse Skin: Nonclassical Dihydrodiol Epoxides" Chemical Research in Toxicology 6
- ^ K.Straif et al. (December 2005) "Carcinogenicity of polycyclic aromatic hydrocarbons" THE LANCET Oncology, vol.6, issue 12
- ^ J.E. Rice et al. (1 December 1987) "Identification of Tumorigenic Metabolites of Benzo[j]fluoranthene Formed in Vivo in Mouse Skin" Cancer Research 47, 6166-6170
- ^ K.Straif et al. (December 2005) "Carcinogenicity of polycyclic aromatic hydrocarbons" The Lancet Oncology, vol.6, issue 12
- ^ Cook, James Wilfred, C. L. Hewett, and I. Hieger. "106. The isolation of a cancer-producing hydrocarbon from coal tar. Parts I, II, and III." Journal of the Chemical Society (1933): 395-405.
- ^ Denissenko, Mikhail F., et al. "Preferential formation of benzo[a]pyrene adducts at lung cancer mutational hotspots in P53." Science 274.5286 (1996): 430-432.
- ISBN 978-1-4613-3772-0
- ^ Denissenko, Mikhail F., et al. "Preferential formation of benzo[a]pyrene adducts at lung cancer mutational hotspots in P53." Science 274.5286 (1996): 430-432.
- ^ Agency for Toxic Substances and Disease Registry (ATSDR). (1995) "Toxicological profile for Polycyclic Aromatic Hydrocarbons (PAHs)" Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service.
- ^ E.J. Lavoie et al. (December 1980) "Identification of Mutagenic Dihydrodiols as Metabolites of Benzo[j]fluoranthene and Benzo[k]fluoranthene" Cancer Research 40, 4528-4532
- ^ Agency for Toxic Substances and Disease Registry (ATSDR). (1995) "Toxicological profile for Polycyclic Aromatic Hydrocarbons (PAHs)" Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service.
- ^ LaVoie, Edmond J., et al. "Tumour initiating activity of dihydrodiols of benzo[b]fluoranthene, benzo[j]fluoranthene, and benzo[k]fluoranthene." Carcinogenesis 3.1 (1982): 49-52.
- ^ Habs, M., D. Schmähl, and J. Misfeld. "Local carcinogenicity of some environmentally relevant polycyclic aromatic hydrocarbons after lifelong topical application to mouse skin." Archiv für Geschwulstforschung 50.3 (1979): 266-274.
- ^ Wynder, Ernest L., and Dietrich Hoffmann. "The carcinogenicity of benzofluoranthenes." Cancer 12.6 (1959): 1194-1199.
- ^ Weyand, E. H., et al. "Effect of fluorine substitution on benzo[j]fluoranthene genotoxicity." Chemico-Biological Interactions 84.1 (1992): 37-53
- ^ Deutsch-Wenzel, Reintraud P., et al. "Experimental studies in rat lungs on the carcinogenicity and dose-response relationships of eight frequently occurring environmental polycyclic aromatic hydrocarbons." Journal of the National Cancer Institute 71.3 (1983): 539-544
- ^ Agency for Toxic Substances and Disease Registry (ATSDR). (1995) "Toxicological profile for Polycyclic Aromatic Hydrocarbons (PAHs)" Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service.