NONMETALLIC ENVIRONMENTAL TOXICANTS

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NON-METALLIC ENVIRONMENTAL TOXICANTS

• SIDNEY GREEN Ph.D
• DEPARTMENT OF PHARMACOLOGY

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ABSORPTION AND DEPOSITION IN THE LUNGS

• Size of particle
  site
• gt5µm upper
  airways
• 1-5µm
  terminal airways or
• 
  alveoli
  
• lt1µm
  suspended in inhaled
• 
  air

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REMOVAL OF PARTICLES

• SITE HOW
  REMOVED
• Unciliated anterior portion wiping, blowing,
  sneezing
• of nose
• posterior portion of nose insoluble
  pharynx and
• 
  swallowed
• 
  soluble pharynx or absorbed
• Tracheobronchial tree cleared by
  upward
• 
  movement of mucus by cilia
• alveolus
  -mucociliary escalator
• 
  -phagocytosis
• 
  -absorbed into lymphatic system

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CHEMICAL CONSTITUTION OF AIR POLLUTION

• Carbon monoxide 52
• Sulfur oxides 18
• Hydrocarbons 12
• Particulate matter 10
• Nitrogen oxides 6

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TYPES OF POLLUTANTS

• Reducing type sulfur dioxide and smoke and by
  fog and cool temperatures
• Oxidizing or photochemical type
  hydrocarbons, oxides of nitrogen and
  photochemical oxidants

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MAJOR SOURCES OF POLLUTANTS

• 5 sources account for 90
• Automobiles
• Industry
• Electric power generation
• Space heating
• Refuse disposal

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HEALTH EFFECTS

• Reducing type acute effects
• Oxidizing or photochemical type allergic
  disorders,
• inflammatory eye disease, acute upper
  respiratory
• infections, influenza and bronchitis

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TOXICOLOGY OF AIR POLLUTANTS

• Sulfur dioxide
• acute toxicity low slight bronchial
  constriction
• chronic (10 ppm for 1-2 months)
• -thickening of mucus layer of trachea
• -bronchial constriction
• -asthmatics more sensitive

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TOXICOLOGY OF AIR POLLUTANTS CONTD

• Sulfuric acid
• sulfur dioxide produces sulfuric acid
• increases airway resistance
• asthmatics more sensitive
• Nitrogen dioxide
• lung irritant
• -pulmonary edema
• -farmers at risk
• -LC50 for 4 hour90ppm
• -2-3 ppm can damage pulmonary function
  lower
• concentrations may affect asthmatics

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OZONE

• Oxidant found at highest concentration in
  atmosphere
• Irritant death from pulmonary edema
• Nitrogen dioxide yields ozone
• Mice 2ppm- gross pulmonary edema
• Chronic exposure to 1ppm causes chronic
  bronchitis, fibrosis and emphysematous changes
• 0.25- 0.75ppm causes shallow rapid breathing,
  decrease in pulmonary compliance
• Sensitivity of lungs to histamine, ACh and
  allergens
• Concentration in urban air similar to that
  causing decline in respiratory function
• Free radical intermediates responsible

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CARBON MONOXIDE

• Colorless,odorless, tasteless and nonirritating
• Most abundant pollutant in lower atmosphere
• Average concentration is 0.1 ppm
• Natural sources account for 90
• -atmospheric oxidation of methane
• -forest fires
• -terpene oxidation
• -ocean (microorganisms)
• Other source is smoking
• -carboxyhemoglobin levels reach 5.9 (heavy
  smokers)

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CARBON MONIXIDE CONTD

• Automobile greatest source of man-made CO
• Natural means of removing CO
• -sinks are reaction of CO with hydroxyl
  radicals to
• form CO2
• -upper atmosphere
• -soil

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TOXICITY OF CO

• Due to combination with hemoglobin yielding COHb
• COHb cannot carry oxygen (first problem)
• Affinity of Hb for CO is 220 x affinity for O2
• Ability of unaltered oxyHb to release O2
  decreases (second problem)
• Also due to direct toxic effect by binding to
  cellular cytochromes of respiratory enzymes and
  myoglobin
• Anemic persons more susceptible and those with
  high metabolic rate

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PATHOLOGY OF ACUTE CO POISONING

• Primarily hemorrhagic subendocardial
  infarctions, and in brain, cerebral edema
• Posthypoxic unconsciousnessgt21 hrs and lt48 years
  old, no complete neurological recovery
• Posthypoxic unconsciousness gt11 hours, and gt48
  years old, complete neurological recovery
• Skin lesions

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DIAGNOSIS OF ACUTE CO POISONING

• Carboxyhemoglobin is cherry-red and gives a red
  color to skin, mucus membrane and finger nails
• In living patient, cherry-red cyanosis is not
  seen usually cyanotic and pale
• Final diagnosis is concentration of
  carboxyhemoglobin if blood

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TREATMENT OF ACUTE CO POISONING

• Fresh air
• Artificial respiration
• Rapid administration of 100 oxygen
• Recovery determined by return of neurological
  function

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TOXICITY OF PROLONGED AND LOW LEVEL EXPOSURE OF CO

• Cardiovascular system heart
• Atherosclerosis
• Behavior vigilance tests
• Teratogenicity neurological and gross brain
  damage
• polycythemia

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ORGANOCHORINE INSECTICIDES

• DDT
• -readily absorbed when dissolved I oils,
  fats,etc.
• -concentrates in adipose tissue
• -crosses placenta
• -bioaccumulates up food chain
• -signs and symptoms of poisoning
• -paresthesias of tongue,lips and face
• -apprehension, hyper susceptibility to
  stimuli, irritability, tremors, tonic and clonic
  convulsion
• -stimulates MFOs
• -weak evidence of carcinogenicity

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CHLORDECONE (KEPONE)

• Extremely persistent, concentrated in food chain
• Stimulates CNS, causes hepatic injury and
  stimulates MFOs
• Causes testicular atrophy and decreased sperm
  count
• Carcinogenic in animals
• Hopewell incident tremors, hepatomegaly, reduced
  sperm counts and motility

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ACUTE TOXICITY OF ORGANOPHOSPHORUS INSECTICIDES

• Muscurinic and nicotinic signs
• Inhalation immediate,orally delayed and
  percutaneously delayed
• Symptoms
• -bronchoconstriction, ocular pain, reduced
  vision
• -GI exposure anorexia, nausea, vomiting,
  cramps
• -time of death may be less than 5 minutes to
  24 hours
• depending on dose, route
• cause of death respiratory failure

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ORGANOPHOSPHORUS INSECTICIDES DIAGNOSIS AND
TREATMENT (ACUTE)

• If suspect determine CHE in erythrocytes and
  plasma
• Atropine in sufficient dose to cross BBB
• Moderate or sever intoxication, pralidoxime
  recommended- 1-2 gms IV
• Supportive measures patent airway, artificial
  respiration, oxygen treatment of shock

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CHRONIC TOXICITY OF ORGANOPHOSPHORUS CMPDS

• Fluorine-containing alkyl phosphates produce a
  delayed type of neurotoxicity
• -not mediated by Ache inhibition
• -it is due to axonal swelling, segmentation
  and
• breakdown into granular debris
• -demyelination due to axonal changes
• -neurotoxic esterase is involved

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FUMIGANTS

• Cyanide
• -one of most rapidly-acting poisons
• -Used to fumigate ships, buildings, soil
• -Found in silver polish, insecticides,
  rodenticides
• -Found in plants, cassava and in seeds of
  apple, apricot, almond
• - Affinity for iron in ferric state
• -Reacts with trivalent iron of cytochromes
  oxidase inhibiting
• respiration In cells
• -Causes transient stage of CNS stimulation
  with hyperpnea
• -Hypoxic convulsions result and usually dies
  from respiratory failure

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TREATMENT OF CYANIDE POISONING

• Treatment should be rapid
• Aimed at preventing binding of cytochromes
  oxidase
• -large pool of ferric iron
• Nitrite used to oxidize hemoglobin to
  methemoglobin (amyl nitrate)

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HERBICIDES

• CHLOROPHENOXY COMPOUNDS
• -2,4,D and 2,4,5 T
• -control broadleaf weeds
• -no accumulation In animal
• -growth hormone for plants
• -death from ventricular fibrillation
  
• -produces chloracne
• -2,3,7,8 TCDD

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PARAQUAT

• Several hundred accidental or suicidal fatalities
  over last 10 years
• Target organs, liver,lungs and kidneys
• -toxic action via superoxide anion radical
• -delayed toxicity in lungs
• -death due to respiratory failure