Benzo[a]pyrene and Polychlorinated Biphenyls

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Structures and Chemical Properties- Consists of aromatic rings- Highly nonpolar

-BaP- May degrade in atmosphere by: UV radiation, NO2, 03 and other oxidants in the atmosphere (Ambe and Mukai 1997)

-PCBs-209 congeners, 1-10 chlorines attached to biphenyl ring- “more chlorines = more hydrophobic, less mobile” -Highly stable-Occurs as liquids or solids-Inflammable (high boiling point)- Insulation properties

Safe 1992

Uses and ApplicationPCBs- Used in industry as a coolants, lubricators, dielectric

insulators (Safe 1992)- Marketed as Aroclor, Clophen etc by chlorine

content (ex. Aroclor 1262)- Produced in the US from 1929-1979

BaP- Found in coal tar, automobile exhaust, burning of

organic material (includes smoke and burned food), fuels (esp. diesal)

Mode of Entry in Aquatic Environment

• PCBs:– Industry use– Improper disposal– Found more in the northern hem than in the southern

(this includes water, air, plankton, fish and marine mammals)

– In 1988, 370 x 103 tons of PCBs were estimated to be present in the environment• ~ 360 x 103 tons retained in coastal sediments

and open ocean water

(Tanabe 1988)

• BaP– Binds to strongly sediment and particulate matter

– Oil (petroleum) spills/leaks (Varanasi and Gmur 1981)

– Combustion (Dusk particles in air…potential for transportation)

– Disposal of fossil fuels and fossil fuel-derived products (Kanaly et al 2000)

Mode of Entry in Aquatic Environment

Chemical Reactivity

• BOTH compounds are highly stable, not very biodegradable, and environmentally persistent! (Cerniglia 1992; Tanabe 1988)

• Lipophilic

• Therefore, have high potential to bioaccumulate through food webs* (Wasserman et al., 1979; Tanabe et al. 1981; Peakall, 1987)

*unless metabolized

Toxicity to Aquatic Life• PCBs:

– Differences depending on the structure, order/placement of chlorines, and number of chlorines• Ex. Planar/nonplanar

– “dioxin like” PCBs• 77*, 81*, 105, 114, 118, 123, 126*, 156, 157, 167, 169*, 189• * = most potent in activating AhR and Cyp1A

http://www.menlh.go.id/apec_vc/osaka/eastjava/hap_en/filter/4.html

Toxicity Equivalent Factors:

TEQ = ∑(C i ×TEFi )n

i =1

US EPA 2009

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Nebert and Dalton 2000

Toxicity to Aquatic Life• BaP:

– Metabolites more toxic than parent compound (Huberman et al 1976; Gelboin 1980)

– Formation of DNA adducts

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Toxic Effects Noted• PCBs

– Wide ranging and varying with species!• Endocrine disruption (Brouwer et al. 1989; Subramanian et al.

1987; Boon et al. 1992)

• Immune suppression (Lahvis et al. 1995; Jepson et al. 1999)

• Reproductive failure (Reijnders 1986)

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• BaP– Skin and scrotal cancer (Slaga et al. 1976) – Lung and colon cancer– Ex. Levels of BaP adducts to DNA in St.

Lawrence beluga brain and liver near those associated with carcinogenis in small laboratory animals (Béland et al. 1993)

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Toxic Effects Noted

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Mode of Entry into Organisms

• Water (passive absorption) (LeBlanc 1995)

• Food – Bioaccumulation– Ex. Western North Pacific estimated

bioconcentration factor of 107 in striped dolphins (Tanabe et al. 1984)

Molecular mode of toxic interaction• Both are metabolized via Cytochrome P450

systems – Oxidative stress

• BaP– “bioactivation”– DNA adducts and binding to cellular

macromolecules• benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE)• Quinones (undergo redox cycling to produce reactive O2

species) (Wood et al 1976)

• Hormone mimics (PCBs)– Hydroxylated PCBs mimic estrogens (Kuiper et al 1998)

– Ex. Changes in human menstral cycles of fish-consumers (Mendola et al. 1997)

Metabolism and Breakdown• PCBs

– VERY SLOW natural breakdown– Metabolism differences depending on the

structure of PCB– Bioaccumulation

• BaP– Fast metabolism– Bacteria breakdown (Kanaley et al 2000)

Defense strategies• PCBs

– Anti-oxidants (Jin et al 2001)

– Adaptation (reduced inducibility)– Hudson River tomcod (Yuan et al. 2006)

• BaP– Epoxide hydrase (formation of diols)– NAD(P)H:quinone oxidoreductase

(Joseph and Jaiswal 1994)

ReferencesPIUSJOSEPHAND ANILK.JAISWAL. 1994. NAD(P)H:quinone oxidoreductase1 (DT diaphorase) specifically preventstheformationofbenzo[a]pyrenequinone-DNAadducts generated by cytochrome P4501A1 and P450 reductase. Proc. Nati.Acad. Sci. USA Vol. 91, pp. 8413-8417

Xiaolei Jin, Sean W. Kennedy, Tamara Di Muccio, and Thomas W. Moon. Role of Oxidative Stress and Antioxidant Defense in 3,3,4,5- Pentachlorobiphenyl-Induced Toxicity and Species-Differential Sensitivity in Chicken and Duck Embryos. Toxicology and Applied Pharmacology 172, 241-248 (2001)

ROBERT A. KANALY, RICHARD BARTHA, KAZUYA WATANABE, AND SHIGEAKI HARAYAMA. 2000. Rapid Mineralization of Benzo[a]pyrene by a Microbial Consortium Growing on Diesel Fuel. APPLIED AND ENVIRONMENTAL MICROBIOLOGY, p. 4205-4211

George G. J. M. Kuiper, Josephine G. Lemmen, Bo Carlsson, J. Christopher Corton, Stephen H. Safe, Paul T. van der Saag, Bart van der Burg and Jan-Åke Gustafsson. 1998. Interaction of Estrogenic Chemicals and Phytoestrogens with Estrogen Receptor ß. Endocrinology Vol. 139, No. 10 4252-4263

Pauline Mendola,Germaine M. Buck, Lowell E. Sever, Maria Zielezny and John E. Vena. 1993. Consumption of PCB-contaminated Freshwater Fish and Shortened Menstrual Cycle Length. Am. J. Epidemiol. 146 (11): 955-960.

Marshall,C.J.,Vousden,K.H.& Philips,D.J.(1984)Nature. (London)310,586-589. Monks,T.J.,Hanzlik,R.P.,Cohen,G.M.,Ross,D.&Graham,D. G. (1992) Toxicol. Appl. Pharmacol. 112, 2-16.

Wood, Levin, Lu, Yagi, Hernandez, Jerina, Conney. 1976. Metabolismof Benzo [czlpyrene and Benzo [a]pyrene Derivatives to Mutagenic Products by Highly Purified Hepatic Microsomal Enzymes. THE JOURNU OF BIOI.O(:ICAI. CHEMISTRY Vol. 51. No. 16. pp. 4882-4890, 19i6

LeBlanc. 1995. Trophic-level Differences in the Bioconcentrrrtion of Chemicals: Implications in Assessing Environmental Biomagification. Environ. Sci. Techno/.1995, 29, 154-160

Tanabe, S., Tanaka, H. & Tatsukawa, R. (I 984). Polychlorobiphenyls, EDDT, and hexachlorocyclohexane isomers in the western North Pacific ecosystem. Arch. Environ. Contarn. Toxicol., 13, 731-8.

Tanabe, S. 1988. PCB Problems in the Future: Foresight from Current Knowledge. Environmental Pollution 50:5-28

References

Pierre Béland, Sylvain DeGuise, Christiane Girard, André Lagacé, Daniel Martineau, Robert Michaud, Derek C.G. Muir, Ross J. Norstrom, Émilien Pelletier, Sankar Ray and Lee R. Shugart. 1993.Toxic Compounds and Health and Reproductive Effects in St. Lawrence Beluga Whales. Journal of Great Lakes ResearchVolume 19, Issue 4, Pages 766-775

Thomas J. Slagaa, Aurora Viajea, David L. Berrya, William Brackena, Steven G. Butyb and John D. Scribnerb. 1976. Skin tumor initiating ability of benzo(a)pyrene 4,5- 7,8- and 7,8-diol-9,10-epoxides and 7,8-diol. Cancer LettersVolume 2, Issue 2, Pages 115-121

Brouwer, A, Reijnders, PJH, Koeman, JH (1989) Polychlorinated biphenyl (PCB)-contaminated fish induces vitamin A and thyroid hormone deficiency in common seal (Phoca vitulina). Aquat Tox 15: 99-106.

Boon, JP, van Arnherm, E, Jansen, S, Kannan, N, Petrick, G, Duinker, JC, Reijnders, PJH, Goksoyr, A. 1992. The toxicokinetics of PCBs in marine mammals with special reference to possible interactions of individual congeners with the cytochrome P450-dependent monooxygenase system: an overview. In: Walker, CH, Livingstone, DR (eds), Persistent Pollutants in Marine Ecosystems. Pergamon, Oxford, pp. 119-159.

Subramanian, A, Tanabe, S, Tatsukawa, R, Miyazaki, N. 1987. Reduction in the testosterone levels by PCBs and DDE in Dall’s porpoises of northwestern North Pacfic. Mar Poll Bull 18(12): 643-646.

Lahvis, GP, Wells, RS, Kuehl, DW, Stewart, JL, Rhinehart, HL, Via, CS. 1995. Decreased lymphocyte responses in free-ranging bottlenose dolphins (Tursiops truncatus) are associated with increased concentrations of PCBs and DDT in peripheral blood. Environ Health Perspect 103:67-72.

Jepson, PD, Bennett, PM, Allchin, CR, Law, RJ, Kuiken, T, Baker, JR, Rogan, E, Kirkwood, JK. 1999. Investigating potential associations between chronic exposure to polychlorinated biphenyls and infectious disease mortality in harbour porpoises from England and Wales. The Sci Total Environ 243/244: 339-348.

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coastal waters. Nature 324: 456-457.

Gelboin,H.V.(1980)Physiol.Rev.60,1107-1166.)

Identification of mutagenic metabolites of benzo(a)pyrene in mammalian cells. 1976. E, Huberman, L Sachs,S K Yang, and V Gelboin. PNAS vol. 73 no. 2 607-611.

Nebert and Dalton. 2006. The role of cytochrome P450 enzymes in endogenous signaling pathways and environmental carcinogenesis. NATURE REVIEWS CANCER. VOLUME 6 947

•(Cerniglia, C. E. 1992. Biodegradation of polycyclic aromatic hydrocarbons. Biodegradation 3:351-368.

Wasserman, M., Wasserman, D., Cucos, S. & Miller, H. J. (1979). World PCB map: Storage and effects in man and his biologic environment in the 1970s. Ann. N. Y. Acad. Sci., 320, 69-1124.

Peakall, D. B. (1987). Accumulation and effects on birds. In: PCBs and the environment, Vol. 2, ed. by J. S. Waid, 31-48. Boca Raton, Florida, CRC Press.

Tanabe, S, Tatsukawa, R, Tanaka, H, Maruyama, K, Miyazaki, N, Fujiyama, T. 1981. Distribution and total burdens of chlorinated hydrocarbons in bodies of striped dolphins (Stenella coeruleoalba). Agr Biol Chem 45(11): 2569-2578.

USHA VARANASJ and DENNIS J. GMUR. 1981. HYDROCARBONS AND METABOLITES IN ENGLISH SOLE (PAROPHRYS VETULUSj EXPOSED SIMULTANEOUSLY TO [3H]BENZO[a]PYRENE AND [14C] CINAPHTHALENEIN OIL-CONTAMINATEDSEDIMENT. AquaticToxicology, 1. pp49-67

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Yoshinari Ambe and Hitoshi Mukai. 1997. LONG TERM STABILITY OF BENZO[a]PYRENE IN STORED ATMOSPHERIC PARTICULATEMATTER SAMPLES. Chemosphere.Vol. 34, Nos 900, pp. 2023-2028.