Chemical and Physical Agents 13.ppt

7/27/2019 Chemical and Physical Agents 13.ppt

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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)

Documents

Chemical and Physical Agents 13.ppt