View
14
Download
0
Category
Preview:
Citation preview
DIOXINAS, FURANOS PCBs
PFOS
2011
2
¿Qué son los COPs?
Tóxicos, Persistentes, Bioacumulables,
Contaminantes globales
Tóxicas: en muy bajas concentraciones afectan la salud de
las personas, animales y el medio ambiente.
Persistentes: tienen muy lenta degradación física, química
o microbiológica.
Bioacumulables: por sus características físico-químicas se
acumulan en tejidos grasos, biomagnificándose al subir en
la cadena alimenticia.
Contaminantes globales: se dispersan por el medio
ambiente por medio de corrientes de aire, marinas, ríos y en
los seres vivos, encontrándose en el agua, sedimentos,
animales y personas incluso en zonas remotas.
3
¿Cuáles son?
• Plaguicidas organoclorados: Aldrin, Clordano,
DDT, Dieldrin, Endrin, Heptacloro,
Hexaclorobenceno, Mirex y Toxafeno,
• Bifenilos Policlorados (PCBs) usado como
aceite dieléctrico en transformadores y
acumuladores y otros usos.
• Dioxinas y Furanos: subproductos no
intencionales generados por combustión y en
algunos procesos industriales cuyos insumos
contienen cloro.
4
Convenio de Estocolmo
Objetivo: Proteger la salud humana y el medio
ambiente frente a los Contaminantes Orgánicos
Persistentes (Art.1)
Chile al ratificarlo se compromete a definir medidas
para reducir y/o eliminar las emisiones derivadas de la
producción y el uso de estas sustancias.
Conama, punto focal del Convenio de Estocolmo
5
Convenio de Estocolmo
Antecedentes Mayo de 2001, Estocolmo, firma del Convenio por
parte de 102 países, incluido Chile.
Mayo de 2004, El Convenio entra en vigor.
Enero de 2005, Es ratificado por Chile (A la fecha111 países lo han ratificado)
Mayo de 2005, Punta del Este Uruguay, se realiza la Primera Conferencia de las Partes
19 de mayo de 2005, Se publica en el Diario Oficial
What Are “Dioxins”?
A family of structurally related chemicals
which have a common mechanism of
action and induce a common spectrum of
biological responses
Dioxins
75 congeners
7 toxic
PCBs
209 congeners
12 toxic
Furans
135 congeners
10 toxic
2,3,7,8-TCDD
1,2,3,7,8-PeCDD
1,2,3,4,7,8-HxCDD
1,2,3,6,7,8-HxCDD
1,2,3,7,8,9-HxCDD
1,2,3,4,6,7,8-HpCDD
1,2,3,4,6,7,8,9-OCDD
2,3,7,8-TCDF
1,2,3,7,8-PeCDF
2,3,4,7,8-PeCDF
1,2,3,4,7,8-HxCDF
1,2,3,6,7,8-HxCDF
1,2,3,7,8,9-HxCDF
2,3,4,6,7,8-HxCDF
1,2,3,4,6,7,8-HpCDF
1,2,3,4,7,8,9-HpCDF
1,2,3,4,6,7,8,9-OCDF
3,3',4,4'-TeCB
3,3',4,4',5-PeCB
3,3',4,4',5,5'-HxCB
Cl
Cl
Cl
Cl
2,3,7,8-Tetrachlorodibenzofuran
O
2,3,7,8-Tetrachlorodibenzo-p-dioxin
Cl
Cl
Cl
Cl
O
O
Cl
Cl
Cl
Cl
Cl
Cl
3,3',4,4',5,5'-Hexachlorobiphenyl
Dioxin-Like Compounds
Dioxinas
Furanos
b
b
b
b
a
a
b
b
Molecular structure of
1,2,3,4,6,7-hexa-CN
Molecular structure of 2,3,7,8-
Tetrachlorodibenzo-p-dioxin
Introduction Methods
9
10
b
b
b
b
a
a
Results
.
SummaryMethods Results
Naftalenos PolNaftalenos Policlorados
2,3,7,8-Tetrachlorodibenzo-p-dioxin
“The Most Toxic Man-Made Compound”
• Prototype for family of structurally related compounds
• Common mechanism of action
• Common spectrum of biological responses
• Environmentally and biologically persistent
(Basis for TEQ approach)
Why the Interest in Dioxins???
• 1899 – ChloracneCharacterized
• 1929 – PCBs produced commercially
• 1947 – “X” Disease in cattle
• 1949 – Nitro, West Virginia
• 1957 – Chick Edema Disease; TCDD identified in TCPs
• 1962-1970 – Agent Orange use in Southeast Asia
• 1968 – “Yusho” oil disease
• 1971 – Times Beach; TCDD causes birth defects in mice
• 1973 – PBB contamination in Michigan
• 1976 – Seveso, Italy
• 1978 – Kociba rat cancer study
• 1979 – “Yucheng” oil dieases
• 1981 – Capacitor fire in Binghamton, NY
• 1985 – 1st US EPA health assessment of TCDD
• 1991 – NIOSH cancer mortality study of US workers
• 1999 – Belgium dioxin poisoning; Viennese poisoning
“Dioxins”Polyhalogenated Dibenzo-p-dioxins and furans
Never produced intentionally
Unwanted byproducts of industrial and combustion
processes
Polyhalogenated Biphenyls, Naphthalenes,
Azo/azoxybenzenes
Commercially produced
Major industrial chemicals
Limited number of congeners have dioxin-like properties
Lateral halogenation
> 3 Halogens
Chlorinated, brominated, and mixed chloro-bromo
congeners
Dioxin-Like Compounds
• Semivolatile
• Lipophilic
• Hydrophobic
• Persistent
• Bioaccumulating
• Toxics
PCBs
• Large Family of Chemicals– 209 Possible Congeners
– Small Subset Are “Dioxins”
– NEVER have PCBS without Dioxin-like
PCBs
• Majority Have Own, Inherent,
Toxicities– Multiple, Overlapping, Structural Classes
– Can Interact Additively, Synergistically,
and/or Antagonistically With Dioxins and
With Other PCB Congeners
TCDD is NEVER Found Alone
• Complex Mixtures Exist both
Environmentally and in Animal and Human
Tissues
• TCDD is only a Small Part of Total
Chemical Mass
• We have the Most Toxicological
Information about TCDD
Toxic Equivalency Factors (TEFs)
• Developed for Risk Assessment
• Interpret Complex Database Derived from Analysis of Samples Containing Mixtures of Dioxin-like Chemicals
• Express Quantitatively the Toxicity of a Chemical in terms of an Equivalent concentration of TCDD (Relative Potency)
• ∑([Chemical] x TEF)PCDD/PCDF/PCB=TEQ
Five Compounds Make up about 80+%
of the Total TEQ in Human Tissues
• Four of 17 Toxic PCDD/PCDF Congeners
– 2,3,7,8-TCDD
– 1,2,4,7,8,-PeCDD
– 1,2,3,6,7,8-HxCDD
– 2,3,4,7,8-PeCDF
• One of the 12 Toxic PCBs
– PCB 126
Major Past Sources of Dioxins (20th
Century Problem)
• Chloralkali Facilities
• Chlorinated herbicide and biocide Production
• Leaded Gasoline
• Municipal, Medical, and Hazardous Waste Incineration
• Chlorine Bleaching of Paper and Pulp Products
Recently Identified Sources
• Open Burning of Household Waste
• Uncontrolled Combustion
– Forest Fires and Volcanos
• Metal Refining
From Factory to the FetusDioxins and PCBs: Pathways of Exposure
and Neurodevelopmental Effects
Dioxins:PVC ManufacturingMedical/Municipal Incinerator
PCBs:TransformersLandfillsHazardous Waste Sites
AIR
SOIL
WATER
FOOD
DioxinsPCBs
PCBs
How do Dioxins Move in the
Environment
• If emitted into air, undergo atmospheric transport
and deposition on land or water
• If emitted into water, bind to sediment
• Recycle in environment
• Bioaccumulate up the food chain
• Resistance to physical, chemical, and biological
degradation
• Dioxins are less mobile than Hg or the more volatile PCBs.
• Dioxins do not appear to exhibit global retort, or
strong “grasshopper” effect.
• Dioxins are continually exchanged among media and
should be viewed as a complex system of stocks and flows
Dioxin Environmental Mobility
Reentrainment
SOURCESTRANSPORT
DEPOSITION
FOOD
SUPPLY
Runoff
Erosion
Combustion
Industrial
Processes
Direct
Discharge
Sources and Pathways to Human Exposures
How are People Exposed?
• Dioxins are omnipresent
• Majority of exposure (>95%) is via microcontamination of food– Meat, fish, dairy
• Sensitive Subpopulations with High Exposure– Subsistence Fishers and Hunters
– Nursing Infants
– Occupational Workers• Oral, dermal, and inhalation exposures
How You are Exposed Makes Little
Difference
• Dioxins are well absorbed from the GI tract and lungs
– Skin absorption is limited and slow
• Dioxins primarily lodge in the liver and fat
• Dioxins are primarily eliminated after metabolism, which is VERY slow
Why do the Body Burdens Increase
Over Time?
• Persistence– Resistance to Biological, Chemical, and Physical
Degradation
– Long Half-Lives in Animals and People• More Body Fat-Longer Half-Life
• Half-Life is Dose-Dependent
• Bioaccumulation– Due to Persistence in Animal tissues Higher Trophic
Organisms have Higher Concentrations
– Older Organisms have Higher Body Burdens than Young
Half-Life Varies with Body Burden
and Body Composition (Emond et al., 2004)
209.79206.29
194.25
157.67
104.17
50.69
27.96
18.6313.57
10.88 9.46 8.71
217.71 215.88212.75
203.00
171.75
114.54
61.50
33.96
22.2918.33 17.2916.58
0.00
50.00
100.00
150.00
200.00
250.00
1.00E-07 1.00E-06 1.00E-05 1.00E-04 1.00E-03 1.00E-02 1.00E-01 1.00E+00 1.00E+01 1.00E+02 1.00E+03
Dose ug/kg de BW
T1
/2 (
da
y)
6.9% FAT
25% FAT
Experimental exposure
Occupational exposure
Background Human exposure
Trace Levels --- Highly Toxic
• Soil, Food --- PPT
• Water --- PPQ
• Air --- fg/m3
• Human Serum ---PPT
• Intake --- 1pg/kg/d TEQ
• Upper Bound Cancer Risk 1x10-3
• Non-Cancer MOE < 10
21%
16%
19%
14%
5%
4%
7%
6%
1%
Soil ingestionSoil dermal contact
Freshwater fish andshellfish
Marine fish and shellfish
Inhalation
Milk
Dairy
Eggs
Beef
Pork
Poultry
Other meats
Vegetable fat
95% of Background Exposure From
Commercial Food Supply
Dioxin/PCB Exposure Trends
• Environmental Levels– Peaked in late ‟60s/early ‟70s – decline since
confirmed by sediment data
– Decline also supported by Emissions Inventory –shows significant decrease from ‟87 to „;95 (~80%)
• Human tissue data suggest mid-90s levels approximately half of 1980– 55 25 ppt TEQ lipid (~5ng/kg ww)
– Decrease continues
• Success of Regulatory Agenda
Dioxin TEQ Levels (PCDDs/PCDFs) in
U.S. Residents Have Fallen from 1960s
(Lorber, 2002)
Mean and Range of TEQs By Age Group
0
5
10
15
20
25
30
35
40
12-19 20-39 40-59 60+
Age Group (Number of Pools)
TE
Q
4.5
6.2
9.0
(17) (13) (10) (11)
13.7
10
6.6
23.5
19.3
15.8
34.4
25.6
41.7
12-19 20-39 40-59 60+
Age Group (years)
(Needham, 2005)
Adverse Effects
Wildlife and Domestic
Animals
Great Lakes fish, birds,
mammals
Baltic seals, Dolphins
Developmental/reproductiv
e effects
Immunological effects
Effects observed at
environmental levels
Cows, Horses, Sheep,
Chickens
Effects observed during
poisoning episodes
Laboratory Animals
Fish
Amphibians
Turtles
Birds
Rats
Mice
Guinea Pigs
Hamsters
Rabbits
Dogs
Non-human primates
Effects of Dioxins
BIOCHEMICAL
• Induction of Drug Metabolizing Genes– Cyp1A1/2, 1B1; GST;
UDPGT; ALDH…
• Induction of Proliferation Genes
• Induction of Cytokines– TNF, IL-6, IL-1β
• Induction of Oxidative Stress
• Induction of Growth factors/receptors– TGFs, EGFR…
• Modulation of Hormones/Receptors
TOXIC
• LethalityWasting
• Gonadal/Lymphoid Atrophy
• Hyperplasia/Metaplasia
• Endocrine Disruption
• Carcinogenicity
• Repro/Developmental toxicity
• Functional Devpt. Toxicity
• Dermal Toxicity
• Immunotoxicity
• Neurotoxicity
• Hepatic Toxicity
• Cardiovascular Toxicity
• Bone/Teeth Toxicity
Effects of Dioxins
• Multiple Effects
• Multiple Tissues
• Both Sexes
• Multiple Species
• Throughout
Vertebrata
• Molecular/
Biochemical
• Metabolic/ Cellular
• Tissue/Organ
• Growth/
Differentiation
• Wasting/Death
Dioxin Effects Require the “Ah
Receptor”
• Highly conserved protein
– throughout Vertebrates
– Related Proteins in Invertebrates
• Member of Growing Family of Key Regulatory
Proteins
– Development, Aging, Hypoxia, Daily Rhythms
• Necessary, but Not Sufficient, for All of the
Effects of Dioxins
DRE TATA
Altered gene expression
TCDD, ...
Co-activators
Co-repressors
Arn
t
hsp90
mRNA
Changes in protein levels
(e.g., CYPIA1, IL-1, ...)
Differentiation
and
Proliferation
Rb, RelA,…HIFa, Sim,...
chromatin
phosphorylation/
dephosphorylation
ClClCl ClO
O
ClClCl ClO
O
ClClCl ClO
O
ClClCl ClO
OArn
t
BT
Fs BT
Fs
hsp90AIP,..
Other Proteins
AIP,..hsp90
Mechanism of Action
Introduction Methods Results
PCNs
Summary
Dioxins‟ Effects in People
• Cardiovascular Disease
• Diabetes
• Cancer
• Porphyria
• Endometriosis
• Decreased Testosterone
• Chloracne
• Biochemical – Enzyme Induction
– Receptor Changes
• Developmental– Thyroid Status
– Immune Status
– Neurobehavior
– Cognition
– Dentition
– Reproductive Effects
– Altered Sex Ratio
– Delayed Breast Devpt
Unfortunate Poisoning Episodes
• PCBs/PCDFs – Japan (“Yusho”)
– Taiwan (“Yucheng”)
• PBBs/PBNs– Michigan
• TCDD– Seveso, Italy
– Vienna, Austria
– Ukraine
• Clear Evidence of Adverse Health Effects
Chloracne
Classic Toxic Effect
• “Hallmark of Dioxin Toxicity”
• High-Dose Response
• Genetic Polymorphism
• Occurs in People, Monkeys, Cows, Rabbits, and Mice
• Associated with multiple problems with skin, teeth, hair and nails following prenatal exposure
La exposición a
dioxinas genera
Cloroacné!
HEALTH EFFECTS IN “HIGHLY”
EXPOSED POPULATIONS
• Exposures Are Not As High As We
Once Thought:10-100X Background
(“Ambient”)
• Occupational Populations
– Chloracne, Cancer, Heart Disease,
Diabetes, ...
• Poisoning Episodes
– Chloracne. Cancer, Heart Disease,
Diabetes, Reproductive,
Developmental, Hormonal and Immune
Effects
EFFECTS SEEN IN ADULTS AT
BACKGROUND EXPOSURES
• Type II Diabetes
– Decreased Glucose Tolerance
– Hyperinsulinemia
– Mechanistic Plausibility
• Endometriosis
– Hormone Disruption and Immune Suppression
– Animal Models
• Cancer????
HEALTH OUTCOMES IN
PRENATALLY-EXPOSED CHILDREN
• Studies in the US (Michigan, North Carolina, Lake Oswego); Japan; the Netherlands; Sweden; Finland
• Low Birthweight
• Cognitive and Behavioral Impairment
• Immune System Effects
• Hormonal Changes (Thyroid Effects)
• Altered Dentition
Dioxin Effects of Greatest
Concern
• Developmental Alterations Occurring at “High End” of Background Population
• Decreased neuro-optimality and IQ
• Altered Behavior
• Altered Immune System
• Altered Hormone Systems
• Altered Growth
ORGANOFLUORINES
F is the most electronegative element. C-F bond
is the strongest of known covalent bonds.
e.g., C-F bond can withstand boiling with 100%
sulfuric acid without any defluorination.
Perfluorinated (fully fluorinated) alkanes are
anthropogenic.
O
C8F17 S - O-
O
PFOS: Perfluorooctanesulfonate
PFOS is the ultimate degradation product of
POSF-based compounds and the compound
found in the environment
-
STRUCTURES OF PERFLUORINATED
SURFACTANTS MONITORED (1)
ORGANOFLUORINE SURFACTANTS
Surfactants: Surface-active agents; due to selective
adsorption at the interface.
Amphiphilic or amphipathic : Implies attraction to two
different kinds of media. Surfactant structure consists
of ‘hydrophilic’ and ‘hydrophobic’ parts.
The hydrophobic portion repels not only water but also
oil and fat. So, fluorinated surfactants exhibit both
water and oil repellency when adsorbed on substrates
such as textiles or paper.
USES OF FLUORINATED
SURFACTANTS (1)
Adhesives, antifogging, antistatic agents, cement
and paint additives, insulators for cables,
electroplating, etching of glass, herbicides and
insecticides, cleaners for hard surfaces (automotive
waxes), cosmetics (hair conditioning formulations).
Fire-Fighting Foams: Formulated to float on
flammable liquids and extinguish flames. FS in
Aqueous Film-Forming Foams (AFFF) reduce the
surface tension of water and form a film on the
fuel surface.
USES OF FLUORINATED
SURFACTANTS (2)
Paper: Used in folding cartons for snack foods,
carry-out fast food, cake mixes, margarine, candy,
bakery products and pet foods.
Polishes, Waxes, Leather: In floor waxes to
provide dust repellency.
Textiles: Carpets, Polyester, etc. to impart soil, oil
and water repellency.
ANALYSIS
Ion-pair extraction (TBA/MTBE)
Betasil- C18 column separation
HPLC-ESMS/MS (triple quadrupole; ES-ve)
Hansen et al. 2001, ES&T, 35, 766-770
Further validation and improvement to accommodate variety of
species/tissues
Sample-Homogenize
: Florisil/carbon column
Location Ringed Gray Seal
Seal
Concentrations (ng/mL) of PFOS
in blood and sera of seals: Spatial differences
Values in brackets are mean; n = 10 to 50
Baltic Sea 16-475 [110] 14-76 [37]
Canadian Arctic <3-12 11-49 [28]
Norwegian Arctic 5-14 [9] NA
PFOS IN POLAR BEARS :
ALASKAN ARCTIC
Liver 82-680 [350] ng/g, wet wt
Blood <2-52 [34] ng/mL
Values in brackets are mean; n = 10 to 40
CONCENTRATIONS (ng/g, wet wt) OF
PFOS IN LIVERS OF COASTAL
AQUATIC MAMMALS
Bottlenose dolphin Florida <75-1520 [490]
Bottlenose dolphin Med.Sea <7-425 [54]
Harbor seal California <4-57 [27]
River dolphin India <35-81
Weddell seal Antarctica <35
Values in brackets are mean; n = 2 to 50
Species n conc.
Salmon andwhitefish liver
15 80
Mink liver 18 2630
Liver-BMF 33
BIOMAGNIFICATION OF PFOS IN MINK
(LIVERS)
Concentrations are in ng/g, wet wt.
ENVIRONMENTAL FATE
PFOS is relatively water soluble, low
vapor pressure and tends to bind to
particulates
While PFOS and related
perfluorinated alkanes are
persistent and can be accumulated
into and retained in biota, their
environmental fate processes are
fundamentally different from
organochlorines and paradigms and
models developed for OCs do not
apply
TOXIC EFFECTS OF PERFLUOROCHEMICALS
Peroxisome proliferation (interference with fatty acid binding and transport)
Mitochondrial bioenergetics (stimulation of mitochondrial respiration)
Inhibits cell-cell communication
Reproductive and developmental effects: rat LD50 = 250 mg/kg
Neuro-endocrinal effects
CONCLUSIONS
PFOS is a ubiquitous global environmental
pollutant: present both in urban and remote
locations. Distribution of PFOA, FOSA and PFHS
is localized.
PFOS bioaccumulates in humans and wildlife;
biomagnifies in the food chain.
Age or sex-related accumulation is not prominent
Transport pathways and environmental fate of
fluorochemicals are the subjects of further/current
investigation.
Recommended