March 31, 1959

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March 31, 1959

• The Dalai Lama, fleeing the Chinese suppression
  of a national uprising in Tibet, crosses the
  border into India, where he is granted political
  asylum.
• Born in Taktser, China, as Tensin Gyatso, he was
  designated the 14th Dalai Lama in 1940, a
  position that eventually made him the religious
  and political leader of Tibet. At the beginning
  of the 20th century, Tibet increasingly came
  under Chinese control, and in 1950 communist
  China invaded the country. After years of
  scattered protests, a full-scale revolt broke out
  in March 1959, and the Dalai Lama was forced to
  flee as the uprising was crushed by Chinese
  troops. On March 31, 1959, he began a permanent
  exile in India, settling at Dharamsala in Punjab,
  where he established a democratically based
  shadow Tibetan government.

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Environmental Occupational Toxic Exposures

• Occupational Toxicology
• This deals with exposure to chemicals found in
  the workplace the major focus involves
  identification of agents of concern, define
  conditions and procedures to allow safe use and
  establish and monitor levels of such agents.
  Under the auspice of OSHA exposure limits of 600
  chemicals is periodically reevaluated.
• Environmental Toxicology
• This deals with the potentially deleterious
  impact of chemicals on living organisms. The
  FAO/WHO organization, JECFA establishes and
  evaluates the acceptable daily intake (ADI) for
  chemicals this is the level of daily ingestion
  that appears to be without risk.

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Threshold limit values of some common air
pollutants

• Ecotoxicology
• As opposed to single individuals this deals with
  the effect of agents on populations and
  communities of living organisms.

TLV-TWA(Time weighted average)concentration for
8-hour workday/40 hour week with out adverse
effects TLV-STE (short term exposure)L maximum
15 minute exposure with out adverse effect
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Toxicological Considerations

• Hazard Risk
• Hazard is the ability of an agent to cause injury
  in a given situation or setting particularly the
  common conditions of use and/or exposure. To
  accurately assess hazard the inherent toxicity
  and the expected level of exposure to an agent
  must be defined.
• Risk is defined as the expected frequency of the
  occurrence of an undesirable effect arising from
  exposure to an agent this requires knowledge of
  dose-response data and often extrapolation from
  known responses and sensitivities to predicted
  exposures.
• Risk Benefit
• Exposure to any agent subjects those exposed to
  risk (remember Paracelsus), to accurately access
  the usefulness of an agent both advantageous and
  adverse effects must be identified, understood
  and in some way quantified to allow an accurate
  assessment of its usability and usefulness. DDT

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• Routes of Exposure
• Industrial and environmental exposures offer
  different routes of exposure, in addition to oral
  ingestion, inhalation and trans-cutaneous
  absorption are more common in industrial
  settings.
• Duration of Exposure
• Toxic reactions may differ qualitatively
  depending on the duration of exposure.
• Acute exposure single or multiple exposures over
  1-2 days
• Chronic exposure multiple exposures over a
  prolonged period of time.

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• Environmental Considerations
• In addition to the direct toxicological effects
  of these agents on organism there are additional
  considerations for environmental toxins
• Stability (degradability) in the environment
  (biotic and/or abiotic)
• Mobility the ability of an agent to move through
  and between the air water and soil.
• Bioaccumulation ingestion of poorly degraded
  agents tends to result in accumulation of agent
  in organisms over time, over a period of time low
  level exposure may accumulate in significant
  levels.
• Biomagnification poorly degraded agents that
  reach minute levels in primary organisms (low on
  the food chain) are accumulated in organisms
  higher on the food chain through consumption
  toxic levels are attained in tertiary consumers.

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Air Pollutants

• Five substances account for 98 of air
  pollution
• Carbon monoxide (52)
• Sulfur oxides (14)
• Hydrocarbons (14)
• Nitrogen oxides (14)
• Particulates (4)

Ozone is a concern in certain areas
situation All air pollutants are inhaled.
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• The majority of these agents are byproducts of
  incomplete combustion of hydrocarbon fuel
  sources, waste disposal also contributes (via
  incineration).
• Ambient air pollution has been implicated as an
  etiologic contributor to the development of
  respiratory diseases (bronchitis, COPD,
  emphysema, asthma and cancer), cardiovascular
  disorders.

In early December of 1952, a cold fog descended
upon London. Because of the cold, Londoners began
to burn more coal than usual. At the same time,
the final conversion of London's electric trams
to diesel buses was completed. The resulting air
pollution was trapped by the heavy layer of cold
air, and the concentration of pollutants built up
dramatically. The smog was so thick that it would
sometimes make driving impossible. It entered
indoors easily, concerts and screenings of films
were cancelled as the audience could not see the
stage or screen.
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• Those with preexisting disorders are at greater
  risk during with exposure to increased levels of
  air pollutants. (London fog 1952, LA)
• Lung function (forced expiratory volume)
  correlates with oxidant levels in ambient air in
  normal lungs.
• Combinations of pollutants produce a synergistic
  detrimental effect on lung function.

Since London was known for its fog, there was no
great panic at the time. In the weeks that
followed, the medical services compiled
statistics and found that the fog had killed
4,000 peoplemost of whom were very young,
elderly, or had pre-existing respiratory
problems. Another 8,000 died in the weeks and
months that followed.
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Carbon monoxide

• This is a colorless, odorless, tasteless,
  nonirritating gas that exists in the atmosphere
  at 1 ppm. It is the product of incomplete
  combustion. It is produced by all forms of
  hydrocarbon combustion and in heavy urban traffic
  can exceed 100 ppm (far above the TLV-TWA.
• Mechanism CO binds reversibly with deoxygenated
  hemoglobin with an affinity 220X greater than O2,
  carboxyhemoglobin (COhgb) is unable to release
  bound oxygen. The delivery of oxygen is greatly
  diminished. The brain and heart are most
  affected. CO may be directly cytotoxic via
  cytochrome binding. Normal COhgb levels are 1
  due to endogenous formation from heme catabolism.
  Smokers routinely exhibit levels of 5-10. At
  1000 ppm (.1) CO 50 of hemoglobin is bound with
  CO. COhgb is bright red, the skin (especially
  lips and mucosal surfaces) appear cherry red.

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• Clinical effects CO intoxication presents with
  the symptoms of hypoxia (usually requires gt15
  COhgb)
• 1. Psychomotor impairment
• 2. Headache, nausea, dizziness, vomiting
• 3, Confusion loss of visual acuity
• 4. Tachycardia, tachypnea, arrhythmias, syncope
  and decreased mentation
• 5. Coma, convulsions, cardiac arrest, shock and
  respiratory failure

Carbon monoxide poisoning. Unenhanced CT scan of
the brain about 16 hours after injury shows
bilaterally symmetrical low attenuation lesions
in the cerebellum (blue arrows), globus pallidus
(red arrows) and caudate nuclei (white arrows).
The patient was in a house fire.
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• The severity of symptoms is dependent on the
  concentration duration of exposure.
• Mild exposure often is misdiagnosed as a viral
  illness. Individuals vary in their response to
  carboxyhemglobiin levels, lt15 is rarely
  symptomatic,
• 40 syncope and collapse occur,
• gt60 is often fatal. The clinical effects may be
  exacerbated by activity, altitude and high
  temperatures.

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• Delayed neuropsychiatric effects may develop
  after exposure and fail to remit.
• Chronic exposure may promote the development of
  ACSVD (chronic smokers, exposure to urban
  traffic, industrial exposure).
• Children and infants are at greater risk due to
  their higher metabolic rate.
• Pregnant women at particular risk due to their
  hypermetabolic state, also fetal hemoglobin binds
  CO with even greater affinity than maternal
  hemoglobin, fetal levels will continue to rise
  after exposure (from mom to fetus).

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• Treatment
• At ambient O2 COhgb has a t1/2 of 320 minutes
• 100 O2 COhgb has a t1/2 of 80 minutes
• At 3 atmospheres (hyperbaric O2) the t1/2 is 23
  minutes
• Fetal t1/2s remain 5 times maternal t1/2s.
• Hyperbaric oxygen treatment is indicated for
  syncope, seizure, COhgb gt25 (gt15 if pregnant),
  cardiac instability coma. Despite the more
  rapid removal of CO hyperbaric treatment has not
  been shown to be definitively more efficacious
  than 100 O2
• A key historical point pets due to their small
  size and higher metabolic rate are often more
  severely affected an illness in both pets and
  owners should bring CO exposure to mind.

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Sulfur Dioxide

• A colorless irritant gas that is a by product of
  sulfur containing fossil fuels (bituminous coal).
• Mechanism of Action
• On contact with moist membranes SO2 forms
  sulfurous acid resulting in severe irritation.
  90 of inhaled SO2 is absorbed in the upper
  respiratory tract where it exerts its most
  deleterious effect. It causes bronchial
  constriction parasympathetic reflexes and smooth
  muscle tone are involved.
• Exposure to 5-10 ppm causes severe bronchospasm
  in normal lungs, 10-20 of healthy individuals
  experience respiratory difficulties at lower
  exposures, asthmatics are particularly at risk.
• There is evidence from chronic industrial
  exposure that some adaptation occurs.
• Symptoms
• Irritation of eyes, nose and throat reflex
  bronchoconstriction. With severe exposure
  delayed onset pulmonary edema may occur. Chronic
  exposure has been associated with aggravation of
  cardiopulmonary disease.

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Nitrogen Oxides

• NO2 is a brownish irritant gas associated with
  fires, it is also formed with fresh silage (green
  fodder stored in a silo) often inducing
  respiratory complaints in farmers (Silo-fillers
  disease).
• Mechanism
• NO2 is a deep lung irritant capable of producing
  pulmonary edema. Symptoms may begin at 25 ppm,
  50 ppm is irritating to the eyes and nose.
  Exposure to 50 ppm for 1 hour can result in
  pulmonary edema and chronic pulmonary lesions.
  100 ppm can cause acute pulmonary edema and
  death.
• Symptoms
• Acute exposure results in irritation of the eyes
  and nose, productive cough, dyspnea and chest
  pain. Pulmonary edema may appear in 1-2 hours.
  In some patients the acute episode is followed by
  a second stage associated with the abrupt onset
  of pulmonary edema and fibrosis of terminal
  bronchioles (bronchiolitis obliterans). Chronic
  exposure at low levels results in emphysematous
  changes.

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Ozone

• O3 is a bluish irritant gas that is produced by
  high voltage electrical equipment, air and water
  purification devices and it is a prominent
  oxidizing component of urban air pollution.
  Respiratory complaints appear directly
  proportional to ozone levels.
• O3 is a mucous membrane irritant. Severe
  exposure causes deep lung irritation and
  pulmonary edema. Penetration into the lungs
  depends on tidal volume the amount of ozone
  reaching the distal respiratory tree is
  significantly increased with exercise. The
  toxicity of O3 results form the formation of
  reactive free radicals.
• Symptoms
• Ozone causes a decrease in pulmonary compliance
  and enhances sensitivity to bronchoconstrictors
  (O3 in combination with other spastic irritants).
  0.1 ppm for 30 minutes causes mild symptoms,
  gt.1 ppm causes decreased visual acuity, chest
  pain and dyspnea. Pulmonary impairment occurs at
  .8 ppm. Airways become inflamed and
  hyper-responsive.
• There is evidence of both direct and secondary
  pulmonary injury resulting in chronic bronchitis,
  bronchiolitis and emphysema.

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Particulate Matter

• Primary particles of PM, such as dust or black
  carbon (soot) are directly emitted into the air
  and come from a variety of sources such as cars,
  trucks with diesel engines, buses, power plants,
  factories, construction sites, tilled fields,
  unpaved roads, stone crushing, and burning of
  wood.
• Secondary particles of PM are formed in the air
  from the chemical change of primary gaseous
  emissions and are formed indirectly when gases
  from burning fuels react with sunlight and water
  vapor. These are formed by fuel combustion.
• Health effects of particulate matter or dust
  inhalation include eye irritation, asthma,
  bronchitis, lung damage, cancer, heavy metal
  poisoning, cardiovascular effects.
• The main effects of dust on health are an
  inflammatory response (chronic irritation) or a
  toxic response.

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• Basically, there are two types of reaction the
  immediate symptoms, and the delayed symptoms
• Immediate symptoms of a respiratory allergy
• Delayed symptoms include headache, dizziness,
  nausea, breathlessness, fever, and vomiting,
  leading to unproductive coughing and breathing
  difficulties. These symptoms usually appear 3 to
  4 hours after exposure, reach a peak in 7 to 8
  hours and disappear after 24 hours.
• Particulates may cause pneumoconiosis
  (silicosos-silicates, asbestosis-asbestos,
  bronchial cancer mesothelioma particularly when
  combined with smoking.
• Particulates also absorb other toxins and deposit
  them in particular areas of the respiratory tree.

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• The most important predictor of the type
  severity of particulate pathology is particle
  size. Smaller particles tend to be more
  injurious.
• Duration of response
• Acute- immediate symptoms
• Subacute- may follow acute symptoms or first
  symtpoms may present days to weeks post exposure,
  dysfunction may be prolonged. Allergy,asthma
• Chronic- may follow early symptoms or first
  symptoms may present weeks/months after exposure,
  almost always associated with permanent
  structural changes (fibrosis) dysfunction

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Other Toxic Gases

• HCN
• Toxicity occurs by inhalation but also by
  ingestion, cutaneous and parenteral exposures.
  There are numerous industrial uses for cyanide
  but these uses are usually well controlled and
  significant exposure occurs only with industrial
  accidents.
• HCN is a common combustion product from fires
  (plastics, polyurethane padding, nylon carpets,
  wool , silk, acrylic tubs and sinks and some
  insulation materials) creating a risk for EMS
  personnel.
• Some pesticides contain cyanide.
• Natural sources include apple seeds and the pits
  of plum, peach, cherry and apricot. Lima beans
  can also be a source of CN. Various nitrile
  compounds release cyanide through liver
  metabolism.
• Classically CN produces an odor described as
  bitter almond, however only 40 of the
  population can detect this odor

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• Mechanism
• CN impairs cytochrome oxidase activity resulting
  in decreased ATP production, decreased O2 use and
  cellular hypoxia. CN is also directly
  neurotoxic.
• CN effects include
• Decreased oxidative metabolism
• Increased glycolysis
• Decreased GABA activity (via decreased GABA
  production).
• CNS damage occurs in the corpus callosum, corpora
  striata, hippocampus and substantia nigra.
• Symptoms
• CNS headache, anxiety, agitation , confusion ,
  lethargy and coma
• CV bradycardia, hypotension
• GI abdominal pain, nausea, vomiting due to
  hemorrhagic gastritis.

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• There is a commercially available CN antidote kit
  which should be administered to those with
  suspected CN exposure. It contains amyl nitrate,
  sodium nitrite and sodium thiosulfate. The goal
  of the kit is to generate methhemoglobin CN has
  a higher affinity for methhemoglobin than
  cytochrome oxidase. The cyanohemoglobin formed
  reacts with a sulfate group to form thiocyanate,
  a non-toxic compound rapidly excreted in the
  urine. EDTA chelates free CN and promotes renal
  excretion.
• Exposure to CN and CO gases often occurs
  concomitantly and separately under the same
  circumstances. CN toxicity should be suspected in
  CO poisoning if they do not respond to 100
  oxygen. The toxicities of CN CO are synergistic.

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• Hydrogen Sulfide
• H2S is a nonflammable, colorless, and denser than
  air gas that tends to accumulate in low-lying
  areas and confined spaces. At low levels it is
  reminiscent of rotten eggs and a slightly higher
  level is an upper airway and pulmonary irritant.
  The development of olfactory fatigue occurs
  acutely putting increasing the risk of toxic
  inhalation, particularly in rescuers.
• H2S is naturally found in crude oil, volcanic
  gas, sewers, hot springs, water treatment plants
  and manure pits.
• Mechanism
• H2S is a cytochrome oxidase inhibitor (similar to
  cyanide)
• Tissue hypoxia leads to cellular hypoxia and
  lactic acidosis

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April 1, 1930

• Leo Hartnett of the Chicago Cubs broke the
  altitude record for a catch by catching a
  baseball dropped from the Goodyear blimp 800 feet
  over Los Angeles.

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• Symptoms H2S is known for its knockdown
  effect unconsciousness can occur after inhaling
  a single breath at 750-1000ppm (due to toxic
  effect at CNS repiratory center
• Low Concentrations
• Headache, vomiting, nausea and fatigue
• High Concentrations
• CNS toxicity dizziness, agitation,
  dyscoordination, somnolence, coma

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• H2S causes CNS pulmonary symptoms
• Pulmonary respiratory depression at 1000ppm,
  acute pulmonary edema ARDS due to irritation of
  terminal bronchioles, impaired ciliary function
  promotes pneumonia.
• Delayed CNS effects
• Hearing dysfunction
• Amnesia and CNS depression
• Motor dysfunction
• Keratoconjunctivitis
• Chronic symptoms can occur at levels 0f 250 ppm.
• Olfactory fatigue occurs at 100 ppm
• EMS and ER personnel are at risk, significant
  exposure can occur from victims clothing and
  transfer by agent via skin contact.

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Table 2 Human health effects at various hydrogen
sulfide concentrations
Hydrogen sulfide is produced in the large
intestine of mammals by metabolism of sulfhydryl
proteins by anaerobic bacteria. The average
levels recorded in intestinal gas have been
between 1.4 and 5.6 mg/m3 (US EPA, 1978
Beauchamp et al., 1984).
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Identification of gases responsible for the odour
ofhuman flatus and evaluation of a device
purportedto reduce this odourF L Suarez, J
Springfield,M D LevittMinneapolis Veterans
Affairs Medical Center, Minneapolis, MN, USAGut
199843100104
The disparity in the production emission of
sulfurous compounds may play a role in certain
cultural tendencies and practices distraction
of the female digit may have greater health
consequences for local populations.
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• Chloramine
• These are chlorinated nitrogen compounds that
  cause rapid injury via inhalation.
  Monochloramine (NH2Cl) dichloramine (NHCl2) are
  the most common. The most common exposure occurs
  when mixing ammonia bleach for cleaning.
• Mechanism
• Inhalation of gas is exposed to moist mucosal
  surfaces resulting in the formation of
  hypochlorous acid, ammonia gas and oxygen free
  radicals.

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• Symptoms
• At low concentrations mild respiratory symptoms
  result, fatalities have resulted from
  bleach/ammonia mixtures in enclosed areas
  (bathrooms). Symptoms may begin long after
  exposure (most within 6 hours, 5-10 onset gt6
  hours).
• SOB
• Wheezing
• Cough
• Chest pain
• Symptoms exacerbated by preexisting respiratory
  problems
• Chemical pneumonitis
• Ocular irritation

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Risk/Benefit Test 2

• Yes Test 2
• Potentially more points

• No Test 2
• Final focused on toxins