ORGANIC CONTAMINANTS By Waqas Azeem

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Organic contaminants are from living sources. Dioxins, PCB, Furans etc.. are some some the example of Organic Contaminants.

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ORGANIC CONTAMINANTS By Waqas Azeem

  1. 1. ORGANIC CONTAMINANTS BY WAQAS AZEEM UNIVERSITY COLLEGE OF AGRICULTURE UNIVERSITY OF SARGODHA
  2. 2. CHEMISTRY Class Ring structure Halide PCBs Single bond Cl PBBs Single bond Br Dioxins Two ether bridges Single bond, Ether bridge Single ring Cl Furans (dibenzo) Pentachlorophenol Cl Cl
  3. 3. FEATURES IN COMMON, ESP. PCBS AND DIOXINS/FURANS ighly lipophilic • bioaccumulation • bioconcentration ersistent organic pollutant • • • • adsorbs onto clay particles sorbs and desorbs on surface of vegetation long-range seasonal transport accumulation in Arctic of organochlorines
  4. 4. FEATURES IN COMMON, ESP. PCBS AND DIOXINS/FURANS tructural similarities lead to similar toxicity profiles among dioxins, furans and some “coplanar” PCBs rincipal toxic outcome in human beings for the class is chloracne • acneiform skin rash, very persistent • preauricular distribution characteristic • refractory to treatment
  5. 5. CHLORACNE AND POLYCYCLIC HALOGENATED ORGANICS hloracne is non-specific: may be cased by • • • • • • polychlorinated dibenzofurans and dioxins polybrominated dibenzofurans and dioxins polychloronaphthalenes polychlorobiphenyls polybromobiphenyls tetrachloroazobenzenes
  6. 6. DIOXINS AND FURANS
  7. 7. DIOXINS AND FURANS omparable toxicity, dioxin > furan oth produced in minute quantities from natural combustion oth produced in significant quantities from • • • • chemical synthesis as contaminant runaway chemical reactions combustion (PVC plastics) effluent (Cl pulp bleaching)
  8. 8. DIOXINS AND FURANS 5 dioxins, 135 furans ono-, di-, octa- chloro dioxins and furans show little toxicity ost toxic of family are: • • • • 2,3,7,8-tetrachlorodibenzodioxin (TCDD) 2,3,7,8-tetrachlorodibenzofuran (TCDF) 1,2,3,7,8-pentachlorodibenzodioxin (PCDD) 2,3,4,7,8-pentachlorodibenzofuran (PCDF)
  9. 9. DIOXINS AND FURANS - FATE AND DISPOSITION hotolysis occurs in sunlight • molecule may be held on surface of plant • light quanta sufficient to break bridging bonds • t1/2 may be only hours in such situations ersistent organic pollutants • persists in soil, t1/2 may be 10 y below surface • fortunately do not migrate well in water • slow photolysis under cold conditions
  10. 10. TOXICOKINETICS OF DIOXINS AND FURANS - 1 ay be absorbed by any route of exposure: • • • • • inhalation ingestion transcutaneous absorption transplacental expressed in breast milk - infants at risk istribution • typical fat depots for lipophilic substance (next)
  11. 11. TOXICOKINETICS OF DIOXINS AND FURANS - 2 istribution (continued) • • • • blocked by BBB, poor entry into brain circulating levels represent what is mobilized from depot may be mobilized with weight loss adipose levels are detectable in individuals without exceptional exposure • adipose levels not routinely used clinical
  12. 12. TOXICOKINETICS OF DIOXINS AND FURANS - 3 etabolism • very slow in vivo • t1/2 approximately 7 years • • • • mostly hepatic Phase I metabolism is hydroxylation or methylation Phase II metabolism is glu, sulf conjugation potent induction of both I and II enzymes
  13. 13. TOXICOKINETICS OF DIOXINS AND FURANS - 4 xcretion • • • • biliary, subject to enterohepatic circulation TCDD metabolites in urine and bile TCDD (unchanged) excreted into bile, enters feces mobilizes into breast milk, which is a significant route of excretion in lactating women
  14. 14. TOXICODYNAMICS OF DIOXINS, FURANS xposure-response ratio for most effects is poorly characterized ery potent (ppq) in animal models uman toxicity • difficult to demonstrate at same exposure levels • appears to be a species difference, Ah receptor affinity ancer risk
  15. 15. MECHANISMS OF TCDD TOXICITY - 1 nteracts with an intracellular receptor: Ah unction of this receptor is probably related to endocrine control mechanisms • • • • estrogenic and thyroid function enzyme induction ? Downregulates tumor suppressor genes modulates protein kinase C, allowing proliferation
  16. 16. MECHANISMS OF TCDD TOXICITY - 2 he Ah receptor • also binds “aryl hydrocarbons”(PAHs) • forms heterodimer with a transport protein: the “aromatic receptor nuclear transporter” (ARNT) • dioxin-Ah-ARNT complex is transported into nucleus • binds there to “dioxin-responsive elements (DREs) (next)
  17. 17. MECHANISMS OF TCDD TOXICITY - 3 n nucleus, dioxin-Ah-ANRT • binds to DRES • activates transcription of a variety of proteins, including cytochromes, cell cycle regulators, cytokines any alleles with different binding efficiencies • probably the explanation for species differences
  18. 18. TOXICITY OF DIOXINS, FURANS on-primate animal models wasting” syndrome epatotoxicity uman studies and primate models hloracne mmunotoxicity Ca risk ematopoietic failure epro toxicity peripheral neuropathy
  19. 19. IMMUNOTOXICITY OF TCDD xtensively studied as a model for immunotoxicology • thymic atrophy • pancytopenia • suppression of cellular immunity o consistent findings or syndrome in humans ay be related to thyroxin-like effects
  20. 20. CANCER RISK ASSOCIATED WITH TCDD ost potent promoter known for rat liver Ca, also potent for lung and skin lassified by IARC as 2B: “possibly” • limited evidence for human carcinogenicity • sufficient evidence for animal carcinogenicity ancers implicated in human studies • soft tissue sarcomas • non-Hodgkins lymphoma
  21. 21. POLYCHLORINATED BIPHENYLS PCBs
  22. 22. PCBS 09 compounds in class, with varied toxicity profiles ay have one to ten chlorines CB formulations are mixtures • 20 PCBs generally present in forumalations • average 3 to 5 chlorines ydrophobic, lipophilic
  23. 23. PCBS any desirable properties • • • • • low flammability electrically nonconductive good heat exchange lubricating solvent an on new manufacture azardous waste, old transformers
  24. 24. PCBS n addition to chlorine substitution, chlorine positioning plays a major role in toxicity: • para: resembles thyroxine • ortho: “non-co-planar” configuration • para, meta: “co-planar” configuration o-planar PCBs resemble TCDD, bind to Ah receptor o-planar → non-co-planar in environment
  25. 25. TOXICOKINETICS OF PCBS bsorption by any route • low volatility but may be adsorbed on particles • heavy skin exposure common in past • transplacental, breast milk important routes istribution • lipophilic, higher %Cl ∝ affinity for adipose • adipose depot • may mobilize with weight loss
  26. 26. TOXICOKINETICS OF PCBS etabolism • • • • primarily hepatic metabolism very slow higher %Cl ∝ resistance to metabolism induction of Phase I, II enzymes xcretion • bile, feces • breast milk
  27. 27. TOXICODYNAMICS OF PCBS eneralizations regarding toxicity: • much less potent than dioxins, furans, by factor of 10,000 or 100,000 • higher chlorine content associated with greater toxicity • coplanar PCBs associated with higher TCDD-like toxicity, activity resembling dioxins and furans • non-coplanar associated with other toxicity
  28. 28. TOXICITY OF PCBS - 1 nimal Models epatotoxicity umans and Primates hloracne europathy epatotoxicity epro effects • hepatocellular injury, possibly jaundice • porphyrin metabolism Ab response Otitis media ancer (hepatic, GI, leukemia,
  29. 29. TOXICITY OF PCBS - 2 oplanar PCBs interact with Ah receptor iotransformation enriches non-co-planar on-coplanar PCBs may show different patterns of toxicity: • • • • neurotoxicity stimulation of insulin release, ↓biosynthesis xenoestrogen effects neutrophil inactivation
  30. 30. TOXICITY OF PCBS - 3 Fish-Eaters” • Great Lakes - Jacobson studies • Sweden, east v. west coast • Netherlands, North Sea onsistent and strongly suggestive • depressed neurocognitive function • associated with PCB-contaminated fish consumption at reasonable amounts
  31. 31. TOXICITY OF PCBS - 4 rganochlorine ecosystem contamination • northern latitudes • susceptible population - Inuit • contaminated fish • marine mammals • breast feeding • elevated rate of otitis media, meningitis • immunsuppression • associated with PCB 77, 126, 169
  32. 32. TOXICITY OF PCBS - 5 reat controversy cotoxicity? • marine mammals • zooplankton and filter feeders ssues arising: • breast feeding • breast cancer • fish advisories
  33. 33. CARCINOGENESIS OF PCBS ighly controversial ARC classifies 2A: “probable” PA, ATSDR treat as human carcinogens vidence suggests certain types: • • • • hepatocellular Ca ?cholangiosarcoma and biliary tract ?leukemia ?non-Hodgkins lymphoma
  34. 34. PROBLEMS IN STUDYING PCBS ost human toxicity information comes from Yusho incident • very high level of exposure • contamination by furans usceptible populations are confounded CBs track with other organochlorines biquitous distribution in industrial society
  35. 35. TOXIC EQUIVALENCY FACTORS ost common system is WHO/IPCS EFs are based on potency compared to 2,3,7,8-TCDD = 1 pplied to PCBs, dioxins, furans, other atabase incomplete, not systematic ost TEFs derive from potency for enzyme induction (CYP1A1)
  36. 36. THE XENOESTROGEN HYPOTHESIS any POPs have weak estrogenic properties, inc. D&Fs, PCBs, pesticides oncern over: • breast Ca • endometriosis • ↓sperm counts, ↑hypospadias hytoestrogens in diet

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