chemical and physical agents 13.ppt
TRANSCRIPT
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Physical and Chemical Agents
of Disease
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Physical Agents of Disease
Heat/Temperature Denature Proteins
Hyperthermia/Hypothermia
Noise Acute and Chronic Damage
Stress
Radiation Ionizing
Alpha particle
Beta Particle
Gamma
X-ray
Non-ionizing Low energy UV light
Microwave
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Electromagnetic Spectrum
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Radiation
The term radiationrefers to Energy
traveling through space. Some types of
radiation associated with radioactivity are
alpha and beta particles and gamma
and X rays.
Radiation also includes neutrons, which
are uncharged.
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Ionizing Radiation
Radiation that . . . has enough energy to
remove tightly bound electronsfrom
atoms, thus creating ions.
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Anthropogenic (man-made)
Sourcesof Ionizing Radiation
X-raysand other procedures used in
medicine (medical tests and therapies)
Radioactive substancesused in industry Cobalt 60/Isomedix
Nuclear powergenerators
Radioactivity(e.g., radioactive fallout) fromthe production and detonation(primarily
for testing purposes) of nuclear weapons.
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Natural Sourcesof
Ionizing Radiation
Cosmic rays
Radiation from geologic formationsthat
contain radioactive elements
(radioelements) such as uranium, from
which radon gasis formed as a decay
product.
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Types of Ionizing Radiation
Particu late energy(e.g., highly energetic
protons, neutrons, and and particles)
Electromagnet ic energy
(e.g. gamma
and X-rays)
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Radioactivity
The spontaneous emission of radiationfrom the nucleus of an unstable atom.
As a result of this emission, the
radioactive atom is converted, ordecays, into an atom of a differentelementthat might or might not beradioactive.
UraniumRadon (gas)Polonium Lead
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Factors that affect the amount of
radiation exposure:
The total amount of time exposedto the
radioactive source Distancefrom the radioactive source
Degree of radioactivity(rate of energy
emission) of a radioactive material Shielding
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Acute Health Effectsof
Ionizing Radiation
At low levels: tissue burns and radiation
sickness (e.g., nausea, weakness, and
loss of hair)
At high levels: capable of producing fatal
injuries
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Stochastic Effects
The term stochast icmeans that there is
an increased probabilityof the
occurrenceof an adverse health event.
Carcinogenesis and genetic damage
such as changes in DNA are possible
stochastic effects of radiation exposure.
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Proportional distribution of the
sources of radiation exposure
Medical
20%
Food/Water
8%
Other Man-
made
1%
Radon
43%
Other Natural
15%
Cosmic
13%
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Uranium
A common elementin the earths crust
Uranium ores uraninite and pitchblende are
found in large amounts in North America,
Africa, and Australia.
Nearly all plants, animals, and aquifers
containtiny amounts of uranium.
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Radon
Inert, colorless, and extremely toxic gas
Produced by the decay of radium and
uranium, which are found universally in
the earths crust in varying amounts.
Classified as a Class A carcinogen
Causes long-term adverse healtheffects
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Extraterrestrial Radiation
Primary cosmic raysoriginate from outer
space (the earths galaxy and the sun).
Cosmic rays have the ability to penetrate
and cross the human body easily.
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Non-Ionizing Radiation
Non -ion izing radiat ionrefers to
Radiation that has enough energy to
move atomsin a molecule around or
cause them to vibrate, but not enough toremove electrons, . . . Examples of this
kind of radiation are sound waves,
visible light, and microwaves.
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Examples of
Non-Ionizing Radiation
Extremely low frequency(ELF) radiation
(high tension power lines)
AM, FM, VHF-TV radio waves
Microwave radiation
Infrared radiation(the source of heat in
heat lamps used for keeping food warm) Visible lightradiation
Ultraviolet radiation(UVA, UVB, UVC)
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Sources of
Ultraviolet Radiation (UVR)
Sources of UVR:
Welders arcs
Tanningbeds
Some flood lampsused in photography
Halogen desk lamps
Lightning
Electrical sparks
Sunbathing
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UVR
UVR coming from the sun is subdivided
into UVA, UVB, and UVC, depending
upon the wave lengthof the light.
Of the three forms of UVR, UVB is
considered to be the form that is most
harmful to health.
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Chemical Agents of Disease
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Benefits of Chemical Use
Increased food production
Improved human health
Better living through chemistry
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Chemical Agents
Acute Exposure
Chronic Exposure
Metabolism/Excretion/Storage
Mixed Function Oxidase (MFOs)
Metallothionins
Cytochrome P450
Kidneys
Lungs (gas or vapor from blood) Skin (water or oils)
Bile Duct (from liver, fat soluble)
Storage in lipids, tissue and bone
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Routes of Exposure
Penetration through the skin
Absorption through the lungs
Absorption through the gastrointestinal tract
Injection
Particulates
>0.01 and
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Particulates and Size The absorption of solid particles, regardless
of solubility, is dependent upon particle size.
Large particles (>5 M)are generallydeposited in the nasopharyngeal(headairways region)region with little absorption.
Particles 2-5 M can penetrate into thetracheobronchialregion.
Very small particles (
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Occupational Lung Diseases
Silicosis
Pneumoconiosis (coal workers, black lung)
Asbestosis
Occupational Asthma
Byssinosis (cotton, flax, hemp)
Chronic Obstructive Pulmonary Disease Chronic Bronchitis
Emphysema
Asthma
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Chemical Harm
Explosive
Flammable
Corrosive Irritants
Allergic response
Toxicity Poisons: LD50 of 50 mg or less per Kg body
weight
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Dose-Response Analysis
Administer different doses of a toxicant to a
large number of subjects and measure theresponse.
Draw a dose-response curve.
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LD50lethal dose the dose that results
in the death of 50% of the subjects
High LD50means low toxicity
Low LD50means high toxicity
LC50
lethal concentration the
environmental concentration that leads to
the death of 50% of the subjects
ED50effective dose the dose thatresults in a measurable effect in 50% of
the subjects
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Necrosisis a progressive failure of
essential metabolic and structural cellcomponents usually in the
cytoplasm. Necrosis generally involves a
group of contiguous cells or occurs at thetissue level. Such progressive
deterioration in structure and function
rapidly leads to cell death or "necroticcells".
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Apoptosis(referred to as "programmed
cell death")is a process of self-destruction
of the cell nucleus. Apoptosis is an
individual or single cell death in that dying
cells are not contiguous but are scatteredthroughout a tissue. Apoptosis is a normal
process in cell turnover in that cells have a
finite lifespan and spontaneously die.
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LD50of some toxicants
LD50 (mg/Kg)Ferrous Sulfate 1500
Morphine 900DDT
Parathion
Vitamin D
100
10
10
Nicotine 1
Botulinus Toxin .00001
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Hazardous Chemical vs.
Hazardous Conditions or Exposure
Chemicals ability to do harm
Ease of contact or exposure (to receptor)
Example: Metal plating operation, bottles of
potassium cyanide, acid spill onto floor
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Pesticides Organochloride
Organophosphate Carbamate
Pyrethroid
Controlling insects:
IPM Use pesticides with highest LC50 that will be effective and apply in a
manner which will not cause impact on non-target organisms
Silent Spring (1962) by Rachel Carson showed the damage that wasbeing done by DDT. Overuse of pesticides will eventually do away with the
songbirds.
Despite opposition, DDT was banned in 1973.
Many other legislative steps were taken to help safeguard the environment.
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Toxicity of metals
Elemental
Inorganic
Organic
Most toxic form is usually the form with thehighest rate of absorption
Toxicity generally increases from elemental(lowest) to inorganic to organic (highest)
Examples : mercuryand lead
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What is the extent of the problem?
Thousands of chemicals are manufactured and released into theenvironment.
Accidental release (eg. Oil spills)
Released on purpose (eg. Pesticides and household products)
Permitted discharges to air, water and soil
historic disposal practices (to land and water) Dilutionis the solution to pollution and out of sight, out of mind
Jackson Twp. Aquifer (1972) contaminated (volatile organics) from disposal of toxicwaste in the Municipal landfill.
Van Dyk Research
Rowe International
Colloid Chemical Leaking underground storage tanks
The toxicity of most of these compounds is unknown.
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Elements, Atoms, & Compounds
There are also millions of chemicalcompounds that have no physiological rolein the body.
More than 6 million different chemicalcompounds are known.
80,000 chemical compounds in household
and industrial use. Thousands of chemicals are synthesizedyearly.
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Identifying Chemicals
The chemical structureshows the arrangementof atoms within a compound.
Chemicals have common names, trade names,technical names, and chemical formulas
associated with them. Manufacturers frequently choose commercial
names for their products.
Chemical formulatells us how many atoms of
each element are contained within a compoundbut does not reveal the arrangement.
Different arrangements = different compounds.
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Variations
of the
formulaC6H8O3
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Assigning Identification
CAS registry numberis the best way to
identify a chemical.
No information about the properties of the
chemical
Designed to eliminate confusion about identity
of the chemical that can arise from multiple
common, trade, and technical names CAS number is observed in scientific literature
and product information (eg MSDS)
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Assigning Identification
Other methodsinclude: RTECS- Registry of Toxic Effects of Chemical
Substances
operated by NIOSH
technical information about commonly usedindustrial chemicals
IUPAC- International Union for Pure and AppliedChemistry
UN IDs- four digit numbers that identify hazardoussubstances and products (such as poisonousmaterials or explosives) of commercial importance
Used in international commerce to label shipping containers
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Concerns
Occupational exposure
Contaminated drinking water
Hazmat spillseffect on responders and
ecosystem
Contaminated air, water, soil, food and
biota
Overuse of pesticides
Terrorismchemical agents
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Chemical Warfare
Some chemicals that are hazardous have
been developed by military organizations
for use in warfare. Examples are:
nerve agents such as sarinand VX,
mustards(blister agents/vesicants) such
as sulfur mustards and nitrogen mustards,
and choking agentssuch as phosgene.
T i S b t F d i
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Toxic Substances Formed in
Nature (some examples):
Red Tides
Paralytic Shellfish Poisoning (PSP) -
saxitoxin
Ciguatera
Botulism Toxin and other microbial toxins
Poison Ivy Venom
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Biotoxins
Biotoxins: Poisons that come from plants or animals
Abrin
Brevetoxin
Colchicine Digitalis
Nicotine
Ricin
Saxitoxinproduced by algae
Strychnine Tetrodotoxin
Trichothecene
http://www.bt.cdc.gov/agent/biotoxins/http://www.bt.cdc.gov/agent/abrin/http://www.bt.cdc.gov/agent/brevetoxin/http://www.bt.cdc.gov/agent/colchicine/http://www.bt.cdc.gov/agent/digitalis/http://www.bt.cdc.gov/agent/nicotine/http://www.bt.cdc.gov/agent/ricin/http://www.bt.cdc.gov/agent/saxitoxin/http://www.bt.cdc.gov/agent/strychnine/http://www.bt.cdc.gov/agent/tetrodotoxin/http://www.bt.cdc.gov/agent/trichothecene/http://www.bt.cdc.gov/agent/trichothecene/http://www.bt.cdc.gov/agent/tetrodotoxin/http://www.bt.cdc.gov/agent/strychnine/http://www.bt.cdc.gov/agent/saxitoxin/http://www.bt.cdc.gov/agent/ricin/http://www.bt.cdc.gov/agent/nicotine/http://www.bt.cdc.gov/agent/digitalis/http://www.bt.cdc.gov/agent/colchicine/http://www.bt.cdc.gov/agent/brevetoxin/http://www.bt.cdc.gov/agent/abrin/http://www.bt.cdc.gov/agent/biotoxins/ -
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SourceTransportReceptor
Evaluating Risk/Exposure
Associated With A ChemicalSource
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Source
Occupational exposure
Contaminated sites
Spill
Air/water discharge
Natural (e.g. Radon)
Transport (mo ement from
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Transport (movement from
sources to receptor)
Soil
Water
Air
Soil gases
Food
Direct contact with source
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Receptor
Inhalation
Dermal contact
Ingestion
Injection
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Pollutants can travel
Water and air movement
Global transport
Pollution is widespread
80% of streams contain at least trace
amounts of some toxicants
USGS 2002
Global Transport of Pollutants
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Global Transport of Pollutants
Gl b l C i C
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Global Convection Currents
Hadley cells: air rises atequator, falls at 30 latitude.
Ferrel cells: air falls
at 30, rises at 60.
Polar cells: air rises
at 60, falls at 90.
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Effects from ChemicalExposures
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Acute Effects
Alteration of vital signs Abnormal skin color
Abnormal skin odor
Excessively dry or moist skin
Miosiscontraction of the pupil
Pupil dilation
Conjunctivitis
Gastrointestinal disorder Central Nervous System disorder
Death
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Chronic Effects
Mutation Cancer
Birth defects
Immunosuppression
Gastrointestinal illness
Hepatic disease Renal disease
Neurological disorders
Skin abnormality
Bioaccumulation
Body weight
Fatty liver
Eventually could lead to early death
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Some Mechanisms of Toxic Effects
Carcinogens
Mutagens
Teratogens
Immune effects
Neurotoxins
Endocrine disruptors
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Carcinogens
Toxicants that cause cancer
Causes uncontrolled cell growth anddivision
Takes a long time for effects to occur Cigarette smoke is the most common
carcinogen
Historically considered the most importanteffect of toxicants
Chemical Induced Carcinogenesis Is
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Chemical-Induced Carcinogenesis Is
a Multistep Process
In i t iat ion - the genotoxic event that leads to mutationsof the DNA and places the affected cells at a greater riskfor tumor formation.
Promot ion - the second step in the carcinogenesis
process, which moves initiated cells further along theirtransformation process. Exposure of initiated cells tochemicals that stimulate cell proliferation, such asirritating substances, results in the production of a cloneof proliferating cells within the tissue.
Progress ion - Progression is the next step toward thetransformation of cells into a tumor that is malignant. Atthis stage in the process, and depending on the particulartissue of origin of the cell, a high growth rate and
invasion into surrounding tissuemay occur.
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Cancer is a Multistep Process
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Mutagens
Toxicants that cause a change in the
genetic sequence.
Can causes cancer or other disorders
Mutations that affect germ cells can be
inherited
The most widely used toxicity test (Ames
test) measures mutagenicity.
Mutations are Changes in the Base-Pair
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Sequence
Mutations Cause Changes in Protein
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Mutations Cause Changes in Protein
Expression
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Teratogens
Toxicant that causes harm to unborn
children
Interferes with normal development
Causes birth defects
Thalidomide
Used as a sleeping pill and to treat nausea in
pregnant women
Caused limb deformities and organ defects
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Immune System Effects
Allergens Toxicants that over-activate the immune
system
Damage is done by the bodys own defenses
Asthma may be stimulated by environmentalallergens
Hypersensitivity
Immune Suppression Some chemicals may suppress the bodys
ability to fight infection
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Immunosuppression by Toxicants
Examples of Chemicals that can suppressthe immune system:
Pharmaceutical compounds such as
corticosteroids and antitumor drugs
Halogenated aromatic hydrocarbons such as
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
Polyaromatic hydrocarbons (PAHs)
Immunosuppression by Toxicants
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Immunosuppression by Toxicants,
cont.
Nitrosamines such as dimethylnitrosamineand diethylnitrosamine.
Pesticides
Metals have been shown to be associatedwith a number of effects on immune function:
As
Be
Cd
Hg
Pb
Examples of Chemical-Induced
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Examples of Chemical Induced
Immunological Disorders
Allergic contact dermatitishas beenassociated with exposures to a number of
different chemicals:
Metals such as platinum, nickel, andchromium
Formaldehyde
Isocyanates such as toluene diisocyanate
Neurotoxins
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Neurotoxins
Toxicants that cause damage to thenervous system
Can cause developmental problems
Heavy metals Lead, Mercury, Cadmium
Pesticides
Organophosphates
Organochlorides
Nerve gas
Sarin
S
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Endocrine System
The endocrine systemis an integrated systemof small organs that involve the release of
extracellular signaling molecules known as
hormones. The endocrine system is instrumental
in regulating metabolism, growth, development
and puberty, tissue function, and also plays a
part in determining mood.[1]The field of
medicinethat deals with disorders of endocrineglands is endocrinology, a branch of the wider
field of internal medicine.
Major endocrine glands. (Maleleft, femaleon the right.) 1.Pineal gland2.
Pituitary gland 3 Thyroid gland 4 Thymus 5 Adrenal gland 6 Pancreas 7
http://en.wikipedia.org/wiki/Hormonehttp://en.wikipedia.org/wiki/Metabolismhttp://en.wikipedia.org/wiki/Human_development_(biology)http://en.wikipedia.org/wiki/Human_development_(biology)http://en.wikipedia.org/wiki/Tissue_(biology)http://en.wikipedia.org/wiki/Moodhttp://en.wikipedia.org/wiki/Medicinehttp://en.wikipedia.org/wiki/Endocrinologyhttp://en.wikipedia.org/wiki/Internal_medicinehttp://en.wikipedia.org/wiki/Internal_medicinehttp://en.wikipedia.org/wiki/Endocrinologyhttp://en.wikipedia.org/wiki/Medicinehttp://en.wikipedia.org/wiki/Moodhttp://en.wikipedia.org/wiki/Tissue_(biology)http://en.wikipedia.org/wiki/Human_development_(biology)http://en.wikipedia.org/wiki/Human_development_(biology)http://en.wikipedia.org/wiki/Metabolismhttp://en.wikipedia.org/wiki/Hormonehttp://en.wikipedia.org/wiki/Malehttp://en.wikipedia.org/wiki/Femalehttp://en.wikipedia.org/wiki/Pineal_glandhttp://en.wikipedia.org/wiki/Pituitary_glandhttp://en.wikipedia.org/wiki/Thyroid_glandhttp://en.wikipedia.org/wiki/Thymushttp://en.wikipedia.org/wiki/Adrenal_glandhttp://en.wikipedia.org/wiki/Pancreashttp://en.wikipedia.org/wiki/Pancreashttp://en.wikipedia.org/wiki/Adrenal_glandhttp://en.wikipedia.org/wiki/Thymushttp://en.wikipedia.org/wiki/Thyroid_glandhttp://en.wikipedia.org/wiki/Pituitary_glandhttp://en.wikipedia.org/wiki/Pineal_glandhttp://en.wikipedia.org/wiki/Femalehttp://en.wikipedia.org/wiki/Male -
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Pituitary gland3.Thyroid gland4.Thymus5.Adrenal gland6.Pancreas7.
Ovary8.Testes
http://en.wikipedia.org/wiki/Pituitary_glandhttp://en.wikipedia.org/wiki/Thyroid_glandhttp://en.wikipedia.org/wiki/Thymushttp://en.wikipedia.org/wiki/Adrenal_glandhttp://en.wikipedia.org/wiki/Pancreashttp://en.wikipedia.org/wiki/Ovaryhttp://en.wikipedia.org/wiki/Testeshttp://en.wikipedia.org/wiki/Image:Illu_endocrine_system.pnghttp://en.wikipedia.org/wiki/Testeshttp://en.wikipedia.org/wiki/Ovaryhttp://en.wikipedia.org/wiki/Pancreashttp://en.wikipedia.org/wiki/Adrenal_glandhttp://en.wikipedia.org/wiki/Thymushttp://en.wikipedia.org/wiki/Thyroid_glandhttp://en.wikipedia.org/wiki/Pituitary_gland -
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The Endocrine system is an informationsignal system much like the nervous
system. However, the nervous system
uses nerves to conduct information,whereas the endocrine system mainly
uses blood vesselsas information
channels.
http://en.wikipedia.org/wiki/Nervous_systemhttp://en.wikipedia.org/wiki/Nervous_systemhttp://en.wikipedia.org/wiki/Blood_vesselshttp://en.wikipedia.org/wiki/Blood_vesselshttp://en.wikipedia.org/wiki/Nervous_systemhttp://en.wikipedia.org/wiki/Nervous_system -
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Glands located in many regions of the
body release into the bloodstreamspecific chemical messengers called
hormones. Hormones regulate the
many and varied functions of an
organism, e.g., mood, growth and
development, tissue function, and
metabolism.
Endocrine Disruptors
http://en.wikipedia.org/wiki/Moodhttp://en.wikipedia.org/wiki/Human_development_(biology)http://en.wikipedia.org/wiki/Human_development_(biology)http://en.wikipedia.org/wiki/Tissue_(biology)http://en.wikipedia.org/wiki/Metabolismhttp://en.wikipedia.org/wiki/Metabolismhttp://en.wikipedia.org/wiki/Tissue_(biology)http://en.wikipedia.org/wiki/Human_development_(biology)http://en.wikipedia.org/wiki/Human_development_(biology)http://en.wikipedia.org/wiki/Mood -
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Endocrine Disruptors
Toxicants that interfere with the normalfunctioning of the bodys hormone system
Often they are toxic at very low
concentrations They can affect:
Reproduction
Development Physiology
Behavior
Hormone
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Hormone
Mimics
Potential Human Reproductive Effects
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Potential Human Reproductive Effects
Feminization
Estrogen mimics
Conversion of testosterone to estrogen
Testicular Cancer
Breast Cancer
Un-descended testicles
Genital birth defects Neurological development
S E d i Di t
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Some Endocrine Disruptors Pesticides
DDT
Endosulfan
Methoxychlor
Highly Chlorinated Compounds PCBs Dioxin
Furans
Alkylphenols and Alkylphenol Ethoxylates Plastic Additives
Bisphenol A
Diethyl Phthalate
Di (2-ethylhexyl) Phthalate
St d i th Eff t f T i t
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Studying the Effects of Toxicants
Difficulties
Determining the history of exposure
Understanding the effects of combined
exposure Effects of individual differences
Human Toxicology
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Human Toxicology
Case Histories Study cases of poisonings
Identifies the effects of acute and high-dose
exposure
Determine the lethal dose
Epidemiology
A statistical approach
Addresses questions of probability and risk
Uses a large sample size
Measures the effect of long-term exposure
Epidemiology (cont )
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Epidemiology (cont.)
Tests real-world conditions
Looks at different end-points than just lethality Hard to determine if the effects are caused by
the condition being studied
Cannot be used to predict the toxicity of newcompounds before they are approved
Case Control Studies
Cohort Studies
Ecological Studies
Intervention Studies
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Intervention Studies
Ethics of using human subjects
Animal models
Mice and rats are commonly used
Mammals
Similar physiology
Other models
Cell cultures
Bacteria
Invertebrates
R l ti f T i C d
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Regulation of Toxic Compounds
FDA Food, Drug and Cosmetic Act
EPA
Federal Insecticide, Fungicide andRodenticide Act (FIFRA)
Toxic Substances Control Act (TSCA)
Resource Conservation and Recovery Act
(RCRA)
OSHA
FIFRA
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FIFRA
EPA is responsible for registering eachnew pesticide that is brought to market.
Risk assessment is based on industry-
supplied research.
The EPA set limits on the pesticides sale
and use.
TSCA
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TSCA
EPA regulates chemicals manufactured in
or imported into the country (~75,000).
Does not cover pesticides, food additives
or drugs.
Screening is minimal.
~10% have been thoroughly tested for toxicity
~2% have been tested for carcinogenicity,
mutagenicity or teratogenicity
Almost none have been tested for endocrine,
nervous or immune system damage
Listing of Hazardous Chemicals
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Listing of Hazardous Chemicals
Many lists exist under both the NJDEP and EPA Visit New Jersey Department of Environmental
Protection (NJDEP) and the Federal Environmental
Protection Agency (EPA) websites to review various
lists.
Residential and Non-Residential Direct Contact
Remediation Standards
Impact to groundwater standards Priority Pollutants List (129)