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

1. ORGANIC CONTAMINANTS
BY
WAQAS AZEEM
UNIVERSITY COLLEGE OF AGRICULTURE
UNIVERSITY OF SARGODHA

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. FEATURES IN COMMON, ESP.
PCBS AND DIOXINS/FURANS
ighly lipophilic
• bioaccumulation
• bioconcentration
ersistent organic pollutant
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adsorbs onto clay particles
sorbs and desorbs on surface of vegetation
long-range seasonal transport
accumulation in Arctic of organochlorines

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. CHLORACNE AND POLYCYCLIC
HALOGENATED ORGANICS
hloracne is non-specific: may be cased by
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polychlorinated dibenzofurans and dioxins
polybrominated dibenzofurans and dioxins
polychloronaphthalenes
polychlorobiphenyls
polybromobiphenyls
tetrachloroazobenzenes

6. DIOXINS AND FURANS

7. DIOXINS AND FURANS
omparable toxicity, dioxin > furan
oth produced in minute quantities from natural combustion
oth produced in significant quantities from
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chemical synthesis as contaminant
runaway chemical reactions
combustion (PVC plastics)
effluent (Cl pulp bleaching)

8. DIOXINS AND FURANS
5 dioxins, 135 furans
ono-, di-, octa- chloro dioxins and furans show little toxicity
ost toxic of family are:
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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. 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. TOXICOKINETICS OF DIOXINS
AND FURANS - 1
ay be absorbed by any route of exposure:
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inhalation
ingestion
transcutaneous absorption
transplacental
expressed in breast milk - infants at risk
istribution
• typical fat depots for lipophilic substance (next)

11. TOXICOKINETICS OF DIOXINS
AND FURANS - 2
istribution (continued)
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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. TOXICOKINETICS OF DIOXINS
AND FURANS - 3
etabolism
• very slow in vivo
• t1/2 approximately 7 years
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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. TOXICOKINETICS OF DIOXINS
AND FURANS - 4
xcretion
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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. 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. MECHANISMS OF TCDD
TOXICITY - 1
nteracts with an intracellular receptor: Ah
unction of this receptor is probably related to endocrine control
mechanisms
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estrogenic and thyroid function
enzyme induction
? Downregulates tumor suppressor genes
modulates protein kinase C, allowing proliferation

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. 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. 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. 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. 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. POLYCHLORINATED BIPHENYLS
PCBs

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. PCBS
any desirable properties
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low flammability
electrically nonconductive
good heat exchange
lubricating
solvent
an on new manufacture
azardous waste, old transformers

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. 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. TOXICOKINETICS OF PCBS
etabolism
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primarily hepatic metabolism
very slow
higher %Cl ∝ resistance to metabolism
induction of Phase I, II enzymes
xcretion
• bile, feces
• breast milk

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. 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. TOXICITY OF PCBS - 2
oplanar PCBs interact with Ah receptor
iotransformation enriches non-co-planar
on-coplanar PCBs may show different patterns of toxicity:
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neurotoxicity
stimulation of insulin release, ↓biosynthesis
xenoestrogen effects
neutrophil inactivation

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. 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. TOXICITY OF PCBS - 5
reat controversy
cotoxicity?
• marine mammals
• zooplankton and filter feeders
ssues arising:
• breast feeding
• breast cancer
• fish advisories

33. CARCINOGENESIS OF PCBS
ighly controversial
ARC classifies 2A: “probable”
PA, ATSDR treat as human carcinogens
vidence suggests certain types:
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hepatocellular Ca
?cholangiosarcoma and biliary tract
?leukemia
?non-Hodgkins lymphoma

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. 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. 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