Toxic chemicals Chapter 17

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Toxic chemicals Chapter 17

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Outline 1. Types of toxic effects 2. Persistent
organic pollutants 3. Toxic metals 4. Chemical
weapon and protection
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1. Types of toxic effects

• Acute toxicity refers to a rapid and serious
  response to a high but short-lived dose.
• Acute poisons interfere with essential
  physiological processes, leading to a variety
  symptoms of distress, even death.
• Chronic toxicity refers to a time-lagged response
  to a relatively low but prolonged exposure.
• Effects are more subtle.
• Set in motion a chain of biochemical events that
  lead to disease states, including cancer.

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Index of acute toxicity LD50
LD50 is the lethal dose for 50 of a population.
Dose is expressed as the weight of a chemical
consumed by an experimental animal per kg of body
weight of the animal.
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LD50 of selected chemicals for rats or mice
Almost every chemical is toxic at some level, and
the difference between toxic and nontoxic
chemicals is a matter of degree.
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Toxicity of Polychlorinates biphenyls

• Less toxic than PCDD/Fs, but more abundant than
  PCDD/Fs in the environment.
• Probable carcinogen
• Cause skin chloracne.
• Learning deficits.

Effects of in utero PCB exposure
Test scores of 4-year-old children vs. PCB
concentrations in the umbilical cord serum at
birth.
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Activation and excretion of carcinogenic
benzanthracene
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Cancer and living conditions
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Hormonal effects
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Dioxins General structures
2. Persistent organic pollutants

• The term dioxins denotes a family of chemical
  compounds, known as polycholorinated
  dibenzo-para-dioxins (PCDDs) and polycholrinated
  dibenzofurans (PCDFs)

General structure
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Dioxins Congeners
Congener a member of the same class, or
group. Each individual PCDD or PCDF is termed a
congener. There are 75 PCDD congeners and 135
PCDF congeners.
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Toxicity of Dioxins

• Extraordinary toxic to lab animals (LD50 in male
  guinea pigs is only 0.6 mg/kg)
• Birth defects
• Cancer
• Skin disorders
• Liver damage
• Suppression of the immune systems
• Variation in toxicity among species is large.
• Male guinea pig, oral, LD50 is 0.6 mg/kg.
• Hamster, intraperitoneum, LD50 is 3000 mg/kg.
• Risk to humans is less clear

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Human risk of dioxin exposure

• USEPA concludes that dioxins likely increase
  cancer incidence.
• WHO classifies 2378-TCDD as a probable human
  carcinogen.
• At high levels, PCDDs cause chloracne, a painful
  skin inflammation.
• Risk from breathing dioxin-laden air is minimal.
• The main exposure route for human is dietary
  (meat, dairy products, and fish). (Due to
  bioaccumulation of dioxins)
• Absorption of dioxins by infant through mothers
  milk is efficient.

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Multiple exposure pathways
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Biochemistry of dioxin toxicity

• PCDD/Fs are planar aromatic molecules.
• The planar structure allows them to bind to Ah
  (Aryl hydrocarbon) receptor protein that is
  present in all animal species.
• The Ah receptor interacts with the cells DNA.
• Dioxin toxicity is roughly proportional to the
  strength of binding to the Ah receptor.
• This explains that 2378-TCDD is the most toxic
  one.

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Dioxin toxicity varies among the congeners
International Toxicity Equivalency Factors (TEF)
for PCDDs and PCDFs
The TEFs allow the conversion of various congener
concentrations into a single toxicity equivalent
quantity (TEQ)
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Dioxin toxicity general rules

• TCDD is the most toxic of the dioxins
• Toxicity decreases when Cl atoms are removed from
  2,3,7,8 positions or added to the remaining
  positions on the rings.
• There are similar toxicity pattern for PCDD and
  PCDF series.

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How much dioxin do we congest?Estimated Dietary
Intakes of PCDD/Fs per day
Source An Assessment of Dioxin Emissions in Hong
Kong, HKEPD, 2000.
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Average content of 2378-TCDD in various foodstuff
(U.S)
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Formation of dioxins

• Combustion
• In any situation where Cl, C, H, and O come into
  contact with heat, PCDD/Fs could be formed as
  trace by-products.
• Dioxin emission correlates with the Cl content of
  the combustion feed.
• Paper pulp bleaching with chlorine
• Chlorine is used to bleach paper pulp.
• PCDDs are formed probably through chlorination of
  the phenolic groups in lignin.
• Manufacture of certain chlorophenol chemicals
• Dioxin was produced as a contaminant of the
  herbicide 2,4,5-T, a component of Agent Orange

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Formation of dioxins in combustion processes

• Incomplete combustion of organic wastes in the
  combustion chamber leads to the formation of
  organic fragments which serve as organic
  precursors to the PCDD/F molecule.
• The waste provides a source of chlorine, and of
  metals. The latter are incorporated into fly ash,
  which carries over to the cooler (250-400oC)
  post-combustion zone of the incineration system.
• The organic precursors adsorb onto the surface of
  the fly ash in the post-combustion zone, and
  following a complex sequence of reactions which
  are catalyzed by metals (primarily copper) in the
  fly ash, lead to the formation of PCDD/Fs along
  with other chlorinated trace organics.

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High-temperature step
PCDF contamination from PCB oxidation
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Agent orange

• 5050 mix of two herbicides 2,4-D and 2,4,5-T.
• Used as a defoliant for broad-leaf trees during
  Vietnam war.
• Contains dioxins as contaminants.
• In 1966, dioxin residues were found in fish,
  shell-fish, and mothers milk in the Vietnam
  target areas.
• In 1978 and 1979, Vietnam veterans in the U.S.
  began complaining of a variety of symptoms such
  as numbness, skin rashes, liver problems, and
  birth defects in their children.

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Dioxin Are there natural sources?

• Analysis of archived UK soil samples dating from
  the pre-1900s confirmed the presence of dioxins.
  (Large scale manufacture and use of chlorinated
  chemicals started after 1900s.)
• Wood burning emits dioxin
• NaCl in wood ? HCl in combustion zone
• Organochlorines are widely produced by a variety
  of microorganisms.

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Polychlorinated biphenyl (PCB)
Excellent insulators, chemically stable, low
flammability and vapor pressure.
Used as coolant in power transformers and
capacitors.

• a total of 209 congeners

• Additional uses
• Heat transfer fluids in machinery
• Plasticizers for PVC and other polymers
• De-inking agents for recycled newspapers

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EPA orders General Electric to dredge PCBs from
Hudson River (Source Pollution Online
newsletter, 12/4/2001) WASHINGTON, Dec 04, 2001
(AP WorldStream via COMTEX) The Bush
administration ordered tons of PCBs removed from
New York's upper Hudson River, setting in motion
one of the largest dredging operations in the
nation's history. General Electric Co. dumped
1.3 million pounds (585,000 kilograms) of PCBs
into the river before the federal government
banned the pollutants in 1977. The company
bitterly opposes dredging, which expected to cost
GE dlrs 500 million. . PCBs, used as insulation
and a coolant, have been linked to cancer in
laboratory animals. The EPA classifies the oily
substance as a probable carcinogen and says PCBs
pose risks to wildlife and to people who eat fish
from the Hudson. GE released PCBs from its
plants in Fort Edward and Hudson Falls, about 40
miles (64 kilometers) north of Albany. The
cleanup will include locations in that stretch,
reaching almost down to the capital city. ..
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3. Toxic metals

• Some metals are essential for the normal
  development and well-being of humans and other
  creatures.
• They include Na, K, Ca, Mg, Cu, Cr, and Zn.
• Other metals are toxic even when present in an
  organism at very low concentrations.
• Examples Antimony, Arsenic, Barium, Beryllium,
  Cadmium, Lead, Mercury, Nickel, Selenium, and
  thallium
• (Arsenic and selenium are not metals but are
  often listed with them).
• The toxic metals can cause brain damage, kidney
  and liver disorders, and bone damage.

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Maximum permissible levels for metals in drinking
water (USEPA standards)
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Biogeochemical cycle of metal species

• All metals cycle naturally through the
  environment.
• Sources weathering of rocks
• Transportation uptake and processing by plants
  and microorganisms.
• Plants living in soils rich in metal species have
  evolved protective mechanisms.
• These plants can be used in remediation of soils
  contaminated with metals.
• Human intervention have greatly perturbed the
  natural biological cycles of the metals.
• Mining and metallurgy
• Coal burning
• Metals can not be broken down into simpler, less
  toxic forms. As a result, they persist in the
  environment and bioaccumulate through food chain.

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Hexavalent Chromium

• Cr (VI) is a carcinogen
• Sources
• Steel-making, cutting, grinding, and welding
• Spills and residues of electroplating baths
• Chromate emissions from cooling towers (used to
  inhibit corrosion)

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Chemical basis for the toxicity of Hg, Cd, and Pb

• All three are soft Lewis acids, i.e., with
  large polarizability.
• They have strong affinity for soft Lewis bases,
  such as the sulfhydryl side chain of cysteine
  residue.
• The heavy metals likely exert their toxic effects
  by tying up critical cysteine residues in
  proteins.

Lewis acid is a species that can form a covalent
bond by accepting an electron pair from another
species. Lewis base is a species that can form a
covalent bond by donating an electron pair to
another species
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Cystein residues provide structurally important
cross-linking sites through formation of
disulfide bridges. Heavy metals interfere with
formation of such bridges.
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Mercury

• When ingested, Hg0, Hg22, and Hg2 are not
  toxic.
• Harmful forms methylmercury ion (CH3)Hg
  regardless of the route of exposure, Hg vapor
  when inhaled.
• (CH3)Hg is produced from mercury ions by
  methanogens living in sediments.
• (CH3)Hg is soluble in water and bioaccumulates
  in the aquatic ecosystem food chain (in
  protein-laden tissues).
• (CH3)Hg binds with protein and peptide
  sulfhydryl groups.
• It is dangerous to eat large quantities of very
  big ocean fish such as tuna and swordfish!

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Mercury sources related to human activities

• Coal-burning (Hg0, Hg2, Hg bound to particulate)
• Chlor-alkali plants
• Hg used as cathode for collecting metallic Na
• Use in electrical devices and equipment, such as
  batteries, switches, lamps
• Use in extracting gold or silver from ores.
• Dental amalgam fillings
• Use of complexes of phenylmercury as paint
  preservatives.
• Organomercurials used as fungicides for seed
  treatment

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Hg pollution long-range transportation

• It has been discovered that fish have elevated Hg
  levels even in lakes remote from any local
  sources.? evidence for the long-range
  transportation of Hg compounds.
• The two volatile forms of Hg, Hgo and dimethyl
  mercury, are responsible via air transportation.
• Both Hgo and dimethyl mercury are formed from
  other Hg species (Hg2 and CH3Hg) through
  bacteria actions.
• Acidic pH favors the formation of CH3Hg over
  (CH3)2Hg? lake acidification would increase
  mercury toxification

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Hg pollution chemistry
Lake acidification would increase mecury
toxification.
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Mercury Poisoning tragedies

• Minamata, Japan,1950s A polyvinyl chloride
  plant released large quantities of Hg compounds
  (used as a catalyst) into Minamata Bay. Many
  residents who relied heavily on fish from the bay
  for their diet became sick. 52 people died and
  many suffered numbness, impaired vision,
  paralysis, and brain damage.
• Iraq, 1972 Wheat grain treated with a methyl
  mercury fungicide was imported as seeds for
  planting. The warning label was in a language the
  Iraqis did not understand. The wheat was used to
  make bread. 500 people died from eating the bread.

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Cadmium

• Cd is chemically similar to Zn.
• It is always found in association with Zn in
  Earths crust, obtained as a side-product of Zn
  mining and extraction.
• It is always present as a contaminant in zinc
  products. (e.g. galvanized steel).
• It is actively taken by many plants since Zn is
  an essential nutrients.

Cd intake by human beings is mainly through food
crops which take up Cd from Cd-laden soils.
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Ouch-ouch disease, irrigation water from a river
contaminated with waste water from a zinc mining
and smelting plant
An Ouch-ouch disease victim
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Source of Cd pollution

• Airborne sources
• Coal burning
• Incineration
• Cement plants
• Phosphate fertilizer Cd is a natural constituent
  of phosphate ore.

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Lead

• Antagonistic (mutually resistant) to the
  essential elements Ca, Fe, I, and possibly Cu.
• Interfere with the incorporation of Fe into
  porphyrin precursors of haem, producing anaemia.
• The metabolism of Pb closely resembles that of Ca
  in many aspects.
• Impair uptake of I by thyroid.

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Source of lead pollution

• Pb-containing paints
• PbCrO4 provides the yellow striping on roads and
  for school buses,
• Pb3O4 is the base for the corrosion-resistant red
  paints on metal structures
• Pb3(OH)2(CO3)2 is a white paint, which was widely
  used as the base of indoor paints
• Leaded gasoline
• Tetraethyl lead is used as gasoline additive to
  improve octane rating

Food and direct ingestion of dust account for
most of the average lead intake by human beings.
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4. Chemical weapon and protection
If you are exposed 1. No hot water! 2. Treat
exposed areas with bleach
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Blister agents
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Blood agents
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Choking agents
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Nerve agents
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